Lee Dupuis | University of Toronto (original) (raw)

Papers by Lee Dupuis

Bone Marrow Transplantation, 2010

Corticosteroids such as methylprednisolone (MP) remain the primary therapy for acute GVHD (aGVHD)... more Corticosteroids such as methylprednisolone (MP) remain the primary therapy for acute GVHD (aGVHD). Patients who are refractory to standard treatment (MP 2 mg/kg/day) may be treated with high-dose MP. This study evaluated the response to high-dose MP in children with aGVHD refractory to standard dose MP. Children who underwent hematopoietic SCT (HSCT) at our hospital between 1 June 2002 and 31 July 2006 and were treated with high-dose MP upon developing steroid-refractory aGVHD were included. Response to aGVHD therapy, adverse effects attributed to MP and overall outcomes were documented. Ten children received high-dose MP (X20 mg/kg/day) on 3-5 consecutive days followed by a tapering dose for steroid-refractory aGVHD, at a median of 12 days after starting standard treatment. Nine patients had Xgrade III aGVHD. Only one patient with grade III aGVHD had a complete response. Two patients had a partial response but flared when MP was tapered. Complications included hypertension (100%), hyperglycemia requiring insulin therapy (33%) and four documented severe infections. Five children (50%) died (median follow-up: 5.9 years). Salvage therapy other than high-dose MP should be considered in children who fail to respond to MP 2 mg/kg/day.

Pharmacotherapy, 2005

The Accreditation Council for Pharmacy Education and the Canadian Council for Accreditation of Ph... more The Accreditation Council for Pharmacy Education and the Canadian Council for Accreditation of Pharmacy Programs state that their respective programs should provide a curriculum appropriate to produce general practitioners of pharmacy. Millions of prescriptions are written for infants and children each year, and relatively few pharmacists practice in environments devoid of pediatric patients. To fulfill the stated mandate, professional pharmacy curricula must include adequate content dedicated to pharmaceutical care of the pediatric patient. Current pediatric curricula are inadequate and must be improved. Pediatric topics should be introduced early in the curriculum to increase students' awareness of the special needs of this vulnerable population. Other recommendations include the provision at least 25 hours of didactic instruction in core pediatric areas and at least one pediatric clinical rotation to all students. Pharmaceutical care of pediatric patients can also be improved by offering pediatric rotations to all pharmacy practice residents and encouraging their participation. However, a change in attitude may be most important. The contention that pediatric pharmacy practice is an isolated subspecialty can no longer be supported.

Therapeutic Drug Monitoring, 2008

Achievement of target trough cyclosporine whole blood concentrations after hematopoietic stem cel... more Achievement of target trough cyclosporine whole blood concentrations after hematopoietic stem cell transplant (HSCT) reduces the risk of acute graft versus host disease (aGvHD). In solid organ transplant, prevention of acute graft rejection correlates with achievement of target area under the whole blood concentration versus time curve during the 12-hour dosing interval (AUC-12) after oral administration. This study describes a limited sampling strategy for determination of cyclosporine AUC-12 after administration of the first intravenous (IV) dose in children undergoing HSCT and explores the relationships between individual whole blood concentrations during the dosing interval and the AUC. Children undergoing HSCT and receiving cyclosporine prophylaxis were eligible to participate. The first cyclosporine dose was given as a 2 hour infusion, and eight cyclosporine concentrations were determined at 2 (end of the infusion), 2.5, 3, 4, 6, 8, 10, and 12 hours after the start of the IV infusion. The relationship between AUC-12 and whole blood cyclosporine concentrations at individual time points after IV administration was assessed by the Spearman rho correlation coefficient. Limited sampling strategies were developed using three to six time points by way of multiple linear regression analysis. The agreement between the AUC-12 calculated using all eight data points and the limited sampling strategies was assessed by intraclass coefficient and Bland-Altman analysis. Twenty-four children (0.5-16.9 yr) participated. The mean AUC-12 calculated using all eight concentration versus time points was 2793 +/- 1165.6 microg/L.hr. Whole blood cyclosporine concentrations obtained within the first 4 hours from the start of the infusion correlated strongly with AUC-12 (Spearman rho coefficient, 0.717-0.868). Limited sampling strategies were developed to estimate AUC-12 with adjusted r2 of 0.955 to 0.998, mean bias of 0% to 0.93%, and precision of 1.6% to 8.1%. The actual AUC-12 and predicted AUC-12 values agreed strongly (intraclass coefficient, 0.981-0.999). Limited sampling strategies using three to six data points have been developed that will estimate cyclosporine AUC-12 after administration of the first IV dose given over 2 hours. Information regarding the possible association between aGvHD and cyclosporine AUC-12 is not available. The limited sampling strategies described here will facilitate the prospective evaluation of the clinical importance of cyclosporine AUC-12 in the prevention of aGvHD.

Supportive Care in Cancer, 2010

We aimed to develop an instrument to assess cancer-treatment-related adverse effects that parents... more We aimed to develop an instrument to assess cancer-treatment-related adverse effects that parents believe children find most bothersome and use it to solicit the opinions of parents regarding this issue. Parents of children 4 to 18 years of age who had received intravenous antineoplastic therapy in the last month were asked to rank prevalence, severity, and degree of bother of each symptom on behalf of their child using a questionnaire. One hundred fifty-eight of 200 (82%) questionnaires were evaluable. The most prevalent symptoms identified were mood swings (85%), fatigue (80%), and disappointment at missing activities with friends/peers (74%). These symptoms were also most commonly identified as being significantly severe. Symptoms most commonly identified as the most bothersome were disappointment at missing activities with friends/peers (50%) and feeling worried about receiving treatment, procedures, or side effects (43%). Symptoms most commonly identified as the most severe and bothersome were disappointment at missing activities with friend/peers (46%); feeling worried about receiving treatment, procedures, or side effects (40%); and painful, aching, or stiff bones, joints, or muscles (36%). This information can be used when explaining the effects of cancer treatment to patients/families, creating policies regarding pediatric cancer care and framing research hypotheses in pediatric supportive care.

Supportive Care in Cancer, 2009

Goals of work Aprepitant is currently recommended for the prevention of acute antineoplastic-indu... more Goals of work Aprepitant is currently recommended for the prevention of acute antineoplastic-induced nausea and vomiting in adults receiving highly emetogenic therapy. The lack of an oral liquid dosage form is one barrier to its use in children. The purpose of this study was to develop a stable oral liquid formulation of aprepitant using the marketed aprepitant capsules. Materials and methods Aprepitant 20-mg/mL oral liquid was prepared from 125-mg capsule contents in Orablend®. Twelve test samples were prepared: six packaged in amber glass and six in polyethylene terephthalate (PET) containers, three of each stored at either 23°C or 4°C. The physical characteristics of the oral aprepitant liquid stored in amber glass bottles were evaluated at the time of compounding and on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, and 91. The aprepitant content of three test solutions of each container type and storage temperature was deter-mined using a stability-indicating assay at 14, 29, 48, 62, 73, and 111 days after compounding. Main results All samples stored in glass demonstrated suitable physical characteristics and those stored in either glass or PET retained more than 94.0% of the initial concentration. Based on the higher limit of the 95% confidence interval of the degradation rate, suspensions stored at 23°C achieved 10% loss within 66 to 85 days, compared to greater than 100 days when stored at 4°C. Conclusions The extemporaneous aprepitant oral suspension formulation described is physically and chemically stable for at least 90 days when refrigerated. The bioavailability of this formulation is unknown.

Biology of Blood and Marrow Transplantation, 2008

We currently calculate area under the busulfan concentration time curve (AUC) using 7 plasma busu... more We currently calculate area under the busulfan concentration time curve (AUC) using 7 plasma busulfan concentrations (AUC7) drawn after the first of 16 i.v. busulfan doses given as a 2-hour infusion every 6 hours. The aim of this study was to develop and validate limited sampling strategies (LSSs) using 3 or fewer busulfan concentration values with which to reliably calculate AUC in children undergoing hematopoietic stem cell transplant (HSCT). Children in the development group (44) received i.v. busulfan at Sick Kids; the validation group consisted of 35 children who received care at CHU Ste-Justine. Busulfan doses given and subsequent plasma busulfan concentrations were recorded. LSSs using 1 to 3 concentration-time points were developed using multiple linear regression. LSS were considered to be acceptable when adjusted r 2 . 0.9, mean bias \15% and precision \15%. Extent of agreement between the AUC7 values and the LSS AUC was assessed by the intraclass correlation coefficient (ICC) and Bland-Altman (BA) analysis. Agreement was considered to be excellent when the lower limit of the 95% confidence limit of the ICC exceeded 0.9 and when the limits of agreement in the BA analysis were ±15% for both AUC and dose. Administration of the theoretic adjusted busulfan doses based on each LSS was simulated and cases where the resulting AUC was .1500 or \900 mM$min were noted. LSSs using 1, 2, or 3 plasma busulfan concentrations were developed that showed excellent agreement with AUC7 and adjusted busulfan doses. In the validation sample, only the 2-and 3-point LSSs demonstrated acceptable precision and lack of bias. LSSs using 2 or 3 plasma busulfan concentrations can be used to reliably estimate busulfan AUC after IV administration in children undergoing HSCT.

Pharmacotherapy, 2010

To evaluate an existing once-daily gentamicin dosing guideline in children with febrile neutropen... more To evaluate an existing once-daily gentamicin dosing guideline in children with febrile neutropenia resulting from antineoplastic therapy and, if necessary, to develop a new simulated dosing guideline that would achieve pharmacokinetic targets more reliably after the first dose. Pharmacokinetic analysis of data from a retrospective medical record review. Hematology-oncology unit of a university-affiliated pediatric hospital in Canada. One hundred eleven patients aged 1-18 years who received once-daily gentamicin between April 2006 and January 2008 for the treatment of febrile neutropenia resulting from antineoplastic therapy, and who had plasma gentamicin concentrations determined after their first dose. Demographic data, gentamicin dosing information, blood sampling times, and plasma gentamicin concentrations were noted. Plasma gentamicin concentrations were determined at approximately 3 and 6 hours after the start of the 30-minute infusion of the first dose. Pharmacokinetic parameters were calculated according to standard first-order, one-compartment equations. The proportion of children who achieved pharmacokinetic targets after the first gentamicin dose was used as a measure of dosing guideline performance; the guideline achieved maximum concentration (C(max)) values below the target range (20-25mg/L) in 51% of patients. Ideal dosing guidelines were then developed using the mean dose required to achieved a C(max) of 23 mg/L for each patient. Univariate analysis or the Student t test was used to determine the existence of significant relationships between pharmacokinetic parameters and patient age and sex. The recursive binary partitioning method was used to determine critical values of age for dosage guideline development; analysis of variance was then used to compare the different levels obtained after use of this technique. Simulated administration of once-daily gentamicin in the following doses achieved a C(max) within or above target in 73% of patients: 1 year to < 6 years, 10.5mg/kg/dose; girls > or = 6 years, 9.5mg/kg/dose; and boys > or = 6 years, 7.5mg/kg/dose. Doses were based on actual body weight for children who weighed less than 125% of ideal body weight or based on effective body weight for children 125% or more of ideal body weight. The initial gentamicin dosing guidelines were not effective in achieving C(max). The new proposed dosing guidelines are predicted to achieve a C(max) within or above the target range in almost three quarters of patients. Subsequent dosing should be tailored according to plasma gentamicin concentrations.

Biology of Blood and Marrow Transplantation

American journal of hospital pharmacy

American Journal of Health-System Pharmacy

ABSTRACT

Clinical pharmacy

The palatability of five flavored and unflavored extemporaneous carbamazepine 20-mg/mL oral suspe... more The palatability of five flavored and unflavored extemporaneous carbamazepine 20-mg/mL oral suspensions was tested, and the bioavailability of the unflavored suspension relative to that of the tablet used in its manufacture was determined in a randomized, crossover study of 12 healthy volunteers. Carbamazepine 400 mg was administered with a glass of water as either 20 mL of unflavored oral suspension (20 mg/mL) or two 200-mg tablets. Subjects were randomly assigned to receive first either the tablets or the suspension in crossover fashion on two days separated by at least two weeks. Blood samples were taken just before and at various times up to 72 hours after the carbamazepine dose. Serum samples were assayed for carbamazepine content by high-performance liquid chromatography. Of five flavored and unflavored carbamazepine suspensions tested in eight volunteers, the cherry-mint formulation was the least palatable. There was no trend in preference among the remaining suspensions (banana, tutti-frutti, grape, and unflavored). Mean values of maximum serum concentration and absorption rate constant were significantly greater for the unflavored suspension (5.7 mg/L [24 mumol/L] and 0.832 hr-1, respectively) than for the tablet (4.9 mg/L [20.8 mumol/L] and 0.266 hr-1, respectively). The mean time to maximum concentration was significantly shorter after suspension administration (3.87 hours) than after tablet administration (11.8 hours). There was no significant difference in the extent of absorption of the tablet and suspension formulation as reflected by the corrected values of the area under the serum concentration-versus-time curves. The mean (+/- S.D.) bioavailability of the suspension relative to the tablet was 94.46% +/- 20.42 (range 76.35-132.72%).(ABSTRACT TRUNCATED AT 250 WORDS)

Annals of allergy

This report describes six children with spina bifida who have experienced a total of 13 episodes ... more This report describes six children with spina bifida who have experienced a total of 13 episodes of generalized hives, angioedema and in two cases, anaphylactoid reactions immediately following saline enema infusions. The enemas were administered using a kit comprised of a plastic bag, tubing, and rectal end-piece. The reactions always occurred with the first use of new kits. A third child developed a systemic reaction with only the rectal end-piece in situ and without infusion of fluid. An in-hospital challenge using a new end-piece in one patient, who was clinically the most sensitive, produced an acute anaphylactoid reaction implicating the end-piece as the most likely source of the problem. The definitive mechanism(s) of the reactions and the agent(s) responsible for them presently remain unknown.

Drug intelligence & clinical pharmacy

This nonblinded, crossover study was undertaken to compare the extent and duration of analgesia a... more This nonblinded, crossover study was undertaken to compare the extent and duration of analgesia after administration of benzydamine 0.15% oral rinse and Hospital for Sick Children (HSC) mouthwash for pain (nystatin 7000 U/ml, lidocaine viscous 0.58 ml/ml in NaCl 0.9%) in pediatric patients with antineoplastic-induced stomatitis. Each mouthwash was administered as a paint or a gargle q2h while the child was awake on two consecutive days. Patients older than three years were asked to describe their pain by means of a pictorial or a visual analog scale. Pain was assessed by the investigator, parent, or nurse caring for the patient as well as the patient whenever possible before each dose and 10, 30, and 60 minutes after the first three doses each day for four days. Stomatitis severity was graded daily. Four patients completed the study protocol; an additional three patients dropped out of the study due to severe stinging when benzydamine oral rinse was administered. The case histories of the patients who completed the study are presented. Both preparations reduced pain for at least one hour in most instances but not for two hours. Three of four patients elected to continue treatment with HSC mouthwash for pain. Study recruitment was halted due to the ethical concern of continuing with the knowledge that benzydamine oral rinse causes oral pain and stinging, especially in patients with severe stomatitis.

American journal of hospital pharmacy

A targeted drug review of cefuroxime use in pediatric patients is described. Because of a 65% inc... more A targeted drug review of cefuroxime use in pediatric patients is described. Because of a 65% increase in cefuroxime costs over one year, pharmacists assessed the appropriateness of cefuroxime therapy from October 13 to December 20, 1987. This assessment was done within 48 hours after the prescription was written and again after 72 hours of cefuroxime therapy, when bacteriology and susceptibility data were available. When a drug order was inappropriate, a pharmacist intervened with the prescribing physician. For comparison, data collection forms were completed for patients who had received cefuroxime before and after the study period. Before the study period, 42% of the cefuroxime orders were inappropriate with respect to dosage or indication at the time of the initial order; this rate fell to 26% during the study period and increased to 33% after the study period. After 72 hours of therapy, the rates of inappropriate prescribing were 48% (before study period), 32% (during study period), and 40% (after study period). During the study period, pharmacists intervened in only half of the 51 cefuroxime orders initially deemed to be inappropriate, and only 26% of these interventions resulted in an order change. Although pharmacists met with some success in increasing the appropriateness of cefuroxime prescribing, both pharmacists and physicians resumed their previous monitoring and prescribing habits after the study period had ended.

DICP: the annals of pharmacotherapy

American Journal of Health-System Pharmacy

Journal of Medical Internet Research

Pain is one of the most common and distressing symptoms reported by adolescents with cancer. Desp... more Pain is one of the most common and distressing symptoms reported by adolescents with cancer. Despite advancements in pain assessment and management research, pain due to cancer and/or its treatments continues to be poorly managed. Our research group has developed a native iPhone application (app) called Pain Squad to tackle the problem of poorly managed pain in the adolescent with cancer group. The app functions as an electronic pain diary and is unique in its ability to collect data on pain intensity, duration, location, and the impact pain has on an adolescent's life (ie, relationships, school work, sleep, mood). It also evaluates medications and other physical and psychological pain management strategies used. Users are prompted twice daily at configurable times to complete 20 questions characterizing their pain and the app transmits results to a database for aggregate reporting through a Web interface. Each diary entry represents a pain case filed by an adolescent with cance...

Pediatric Drugs, 2010

Existing guidelines for the prevention of antineoplastic chemotherapy-induced nausea and vomiting... more Existing guidelines for the prevention of antineoplastic chemotherapy-induced nausea and vomiting (CINV) in children are constrained by the lack of robust evidence. Current guidelines recommend the use of a serotonin 5-HT(3) receptor antagonist plus a corticosteroid to prevent acute CINV. Consequently, antiemetic agents that are recommended for use in adult cancer patients do not appear in the current pediatric guidelines. In addition, there is no information to guide the selection of alternative antiemetic agents for children who either cannot receive the recommended agents or who do not respond adequately to the treatment. Possible barriers to adherence to the pediatric antiemetic selection guidelines that are currently available are discussed, and published pediatric experience with antiemetic agents recommended in the current adult antiemetic selection guidelines (dolasetron, tropisetron, palonosetron, aprepitant) is summarized in this review. The use of novel and emerging antiemetic therapeutic interventions {metopimazine, diphenhydramine (Benadryl)-lorazepam (Avitan)-dexamethasone (Decadron) [BAD], nabilone, acupuncture, midazolam, olanzapine, mirtazapine, gabapentin, droperidol} in children are explored.

Journal of the American Academy of Dermatology, 1985

Bone Marrow Transplantation, 2010

Corticosteroids such as methylprednisolone (MP) remain the primary therapy for acute GVHD (aGVHD)... more Corticosteroids such as methylprednisolone (MP) remain the primary therapy for acute GVHD (aGVHD). Patients who are refractory to standard treatment (MP 2 mg/kg/day) may be treated with high-dose MP. This study evaluated the response to high-dose MP in children with aGVHD refractory to standard dose MP. Children who underwent hematopoietic SCT (HSCT) at our hospital between 1 June 2002 and 31 July 2006 and were treated with high-dose MP upon developing steroid-refractory aGVHD were included. Response to aGVHD therapy, adverse effects attributed to MP and overall outcomes were documented. Ten children received high-dose MP (X20 mg/kg/day) on 3-5 consecutive days followed by a tapering dose for steroid-refractory aGVHD, at a median of 12 days after starting standard treatment. Nine patients had Xgrade III aGVHD. Only one patient with grade III aGVHD had a complete response. Two patients had a partial response but flared when MP was tapered. Complications included hypertension (100%), hyperglycemia requiring insulin therapy (33%) and four documented severe infections. Five children (50%) died (median follow-up: 5.9 years). Salvage therapy other than high-dose MP should be considered in children who fail to respond to MP 2 mg/kg/day.

Pharmacotherapy, 2005

The Accreditation Council for Pharmacy Education and the Canadian Council for Accreditation of Ph... more The Accreditation Council for Pharmacy Education and the Canadian Council for Accreditation of Pharmacy Programs state that their respective programs should provide a curriculum appropriate to produce general practitioners of pharmacy. Millions of prescriptions are written for infants and children each year, and relatively few pharmacists practice in environments devoid of pediatric patients. To fulfill the stated mandate, professional pharmacy curricula must include adequate content dedicated to pharmaceutical care of the pediatric patient. Current pediatric curricula are inadequate and must be improved. Pediatric topics should be introduced early in the curriculum to increase students' awareness of the special needs of this vulnerable population. Other recommendations include the provision at least 25 hours of didactic instruction in core pediatric areas and at least one pediatric clinical rotation to all students. Pharmaceutical care of pediatric patients can also be improved by offering pediatric rotations to all pharmacy practice residents and encouraging their participation. However, a change in attitude may be most important. The contention that pediatric pharmacy practice is an isolated subspecialty can no longer be supported.

Therapeutic Drug Monitoring, 2008

Achievement of target trough cyclosporine whole blood concentrations after hematopoietic stem cel... more Achievement of target trough cyclosporine whole blood concentrations after hematopoietic stem cell transplant (HSCT) reduces the risk of acute graft versus host disease (aGvHD). In solid organ transplant, prevention of acute graft rejection correlates with achievement of target area under the whole blood concentration versus time curve during the 12-hour dosing interval (AUC-12) after oral administration. This study describes a limited sampling strategy for determination of cyclosporine AUC-12 after administration of the first intravenous (IV) dose in children undergoing HSCT and explores the relationships between individual whole blood concentrations during the dosing interval and the AUC. Children undergoing HSCT and receiving cyclosporine prophylaxis were eligible to participate. The first cyclosporine dose was given as a 2 hour infusion, and eight cyclosporine concentrations were determined at 2 (end of the infusion), 2.5, 3, 4, 6, 8, 10, and 12 hours after the start of the IV infusion. The relationship between AUC-12 and whole blood cyclosporine concentrations at individual time points after IV administration was assessed by the Spearman rho correlation coefficient. Limited sampling strategies were developed using three to six time points by way of multiple linear regression analysis. The agreement between the AUC-12 calculated using all eight data points and the limited sampling strategies was assessed by intraclass coefficient and Bland-Altman analysis. Twenty-four children (0.5-16.9 yr) participated. The mean AUC-12 calculated using all eight concentration versus time points was 2793 +/- 1165.6 microg/L.hr. Whole blood cyclosporine concentrations obtained within the first 4 hours from the start of the infusion correlated strongly with AUC-12 (Spearman rho coefficient, 0.717-0.868). Limited sampling strategies were developed to estimate AUC-12 with adjusted r2 of 0.955 to 0.998, mean bias of 0% to 0.93%, and precision of 1.6% to 8.1%. The actual AUC-12 and predicted AUC-12 values agreed strongly (intraclass coefficient, 0.981-0.999). Limited sampling strategies using three to six data points have been developed that will estimate cyclosporine AUC-12 after administration of the first IV dose given over 2 hours. Information regarding the possible association between aGvHD and cyclosporine AUC-12 is not available. The limited sampling strategies described here will facilitate the prospective evaluation of the clinical importance of cyclosporine AUC-12 in the prevention of aGvHD.

Supportive Care in Cancer, 2010

We aimed to develop an instrument to assess cancer-treatment-related adverse effects that parents... more We aimed to develop an instrument to assess cancer-treatment-related adverse effects that parents believe children find most bothersome and use it to solicit the opinions of parents regarding this issue. Parents of children 4 to 18 years of age who had received intravenous antineoplastic therapy in the last month were asked to rank prevalence, severity, and degree of bother of each symptom on behalf of their child using a questionnaire. One hundred fifty-eight of 200 (82%) questionnaires were evaluable. The most prevalent symptoms identified were mood swings (85%), fatigue (80%), and disappointment at missing activities with friends/peers (74%). These symptoms were also most commonly identified as being significantly severe. Symptoms most commonly identified as the most bothersome were disappointment at missing activities with friends/peers (50%) and feeling worried about receiving treatment, procedures, or side effects (43%). Symptoms most commonly identified as the most severe and bothersome were disappointment at missing activities with friend/peers (46%); feeling worried about receiving treatment, procedures, or side effects (40%); and painful, aching, or stiff bones, joints, or muscles (36%). This information can be used when explaining the effects of cancer treatment to patients/families, creating policies regarding pediatric cancer care and framing research hypotheses in pediatric supportive care.

Supportive Care in Cancer, 2009

Goals of work Aprepitant is currently recommended for the prevention of acute antineoplastic-indu... more Goals of work Aprepitant is currently recommended for the prevention of acute antineoplastic-induced nausea and vomiting in adults receiving highly emetogenic therapy. The lack of an oral liquid dosage form is one barrier to its use in children. The purpose of this study was to develop a stable oral liquid formulation of aprepitant using the marketed aprepitant capsules. Materials and methods Aprepitant 20-mg/mL oral liquid was prepared from 125-mg capsule contents in Orablend®. Twelve test samples were prepared: six packaged in amber glass and six in polyethylene terephthalate (PET) containers, three of each stored at either 23°C or 4°C. The physical characteristics of the oral aprepitant liquid stored in amber glass bottles were evaluated at the time of compounding and on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, and 91. The aprepitant content of three test solutions of each container type and storage temperature was deter-mined using a stability-indicating assay at 14, 29, 48, 62, 73, and 111 days after compounding. Main results All samples stored in glass demonstrated suitable physical characteristics and those stored in either glass or PET retained more than 94.0% of the initial concentration. Based on the higher limit of the 95% confidence interval of the degradation rate, suspensions stored at 23°C achieved 10% loss within 66 to 85 days, compared to greater than 100 days when stored at 4°C. Conclusions The extemporaneous aprepitant oral suspension formulation described is physically and chemically stable for at least 90 days when refrigerated. The bioavailability of this formulation is unknown.

Biology of Blood and Marrow Transplantation, 2008

We currently calculate area under the busulfan concentration time curve (AUC) using 7 plasma busu... more We currently calculate area under the busulfan concentration time curve (AUC) using 7 plasma busulfan concentrations (AUC7) drawn after the first of 16 i.v. busulfan doses given as a 2-hour infusion every 6 hours. The aim of this study was to develop and validate limited sampling strategies (LSSs) using 3 or fewer busulfan concentration values with which to reliably calculate AUC in children undergoing hematopoietic stem cell transplant (HSCT). Children in the development group (44) received i.v. busulfan at Sick Kids; the validation group consisted of 35 children who received care at CHU Ste-Justine. Busulfan doses given and subsequent plasma busulfan concentrations were recorded. LSSs using 1 to 3 concentration-time points were developed using multiple linear regression. LSS were considered to be acceptable when adjusted r 2 . 0.9, mean bias \15% and precision \15%. Extent of agreement between the AUC7 values and the LSS AUC was assessed by the intraclass correlation coefficient (ICC) and Bland-Altman (BA) analysis. Agreement was considered to be excellent when the lower limit of the 95% confidence limit of the ICC exceeded 0.9 and when the limits of agreement in the BA analysis were ±15% for both AUC and dose. Administration of the theoretic adjusted busulfan doses based on each LSS was simulated and cases where the resulting AUC was .1500 or \900 mM$min were noted. LSSs using 1, 2, or 3 plasma busulfan concentrations were developed that showed excellent agreement with AUC7 and adjusted busulfan doses. In the validation sample, only the 2-and 3-point LSSs demonstrated acceptable precision and lack of bias. LSSs using 2 or 3 plasma busulfan concentrations can be used to reliably estimate busulfan AUC after IV administration in children undergoing HSCT.

Pharmacotherapy, 2010

To evaluate an existing once-daily gentamicin dosing guideline in children with febrile neutropen... more To evaluate an existing once-daily gentamicin dosing guideline in children with febrile neutropenia resulting from antineoplastic therapy and, if necessary, to develop a new simulated dosing guideline that would achieve pharmacokinetic targets more reliably after the first dose. Pharmacokinetic analysis of data from a retrospective medical record review. Hematology-oncology unit of a university-affiliated pediatric hospital in Canada. One hundred eleven patients aged 1-18 years who received once-daily gentamicin between April 2006 and January 2008 for the treatment of febrile neutropenia resulting from antineoplastic therapy, and who had plasma gentamicin concentrations determined after their first dose. Demographic data, gentamicin dosing information, blood sampling times, and plasma gentamicin concentrations were noted. Plasma gentamicin concentrations were determined at approximately 3 and 6 hours after the start of the 30-minute infusion of the first dose. Pharmacokinetic parameters were calculated according to standard first-order, one-compartment equations. The proportion of children who achieved pharmacokinetic targets after the first gentamicin dose was used as a measure of dosing guideline performance; the guideline achieved maximum concentration (C(max)) values below the target range (20-25mg/L) in 51% of patients. Ideal dosing guidelines were then developed using the mean dose required to achieved a C(max) of 23 mg/L for each patient. Univariate analysis or the Student t test was used to determine the existence of significant relationships between pharmacokinetic parameters and patient age and sex. The recursive binary partitioning method was used to determine critical values of age for dosage guideline development; analysis of variance was then used to compare the different levels obtained after use of this technique. Simulated administration of once-daily gentamicin in the following doses achieved a C(max) within or above target in 73% of patients: 1 year to < 6 years, 10.5mg/kg/dose; girls > or = 6 years, 9.5mg/kg/dose; and boys > or = 6 years, 7.5mg/kg/dose. Doses were based on actual body weight for children who weighed less than 125% of ideal body weight or based on effective body weight for children 125% or more of ideal body weight. The initial gentamicin dosing guidelines were not effective in achieving C(max). The new proposed dosing guidelines are predicted to achieve a C(max) within or above the target range in almost three quarters of patients. Subsequent dosing should be tailored according to plasma gentamicin concentrations.

Biology of Blood and Marrow Transplantation

American journal of hospital pharmacy

American Journal of Health-System Pharmacy

ABSTRACT

Clinical pharmacy

The palatability of five flavored and unflavored extemporaneous carbamazepine 20-mg/mL oral suspe... more The palatability of five flavored and unflavored extemporaneous carbamazepine 20-mg/mL oral suspensions was tested, and the bioavailability of the unflavored suspension relative to that of the tablet used in its manufacture was determined in a randomized, crossover study of 12 healthy volunteers. Carbamazepine 400 mg was administered with a glass of water as either 20 mL of unflavored oral suspension (20 mg/mL) or two 200-mg tablets. Subjects were randomly assigned to receive first either the tablets or the suspension in crossover fashion on two days separated by at least two weeks. Blood samples were taken just before and at various times up to 72 hours after the carbamazepine dose. Serum samples were assayed for carbamazepine content by high-performance liquid chromatography. Of five flavored and unflavored carbamazepine suspensions tested in eight volunteers, the cherry-mint formulation was the least palatable. There was no trend in preference among the remaining suspensions (banana, tutti-frutti, grape, and unflavored). Mean values of maximum serum concentration and absorption rate constant were significantly greater for the unflavored suspension (5.7 mg/L [24 mumol/L] and 0.832 hr-1, respectively) than for the tablet (4.9 mg/L [20.8 mumol/L] and 0.266 hr-1, respectively). The mean time to maximum concentration was significantly shorter after suspension administration (3.87 hours) than after tablet administration (11.8 hours). There was no significant difference in the extent of absorption of the tablet and suspension formulation as reflected by the corrected values of the area under the serum concentration-versus-time curves. The mean (+/- S.D.) bioavailability of the suspension relative to the tablet was 94.46% +/- 20.42 (range 76.35-132.72%).(ABSTRACT TRUNCATED AT 250 WORDS)

Annals of allergy

This report describes six children with spina bifida who have experienced a total of 13 episodes ... more This report describes six children with spina bifida who have experienced a total of 13 episodes of generalized hives, angioedema and in two cases, anaphylactoid reactions immediately following saline enema infusions. The enemas were administered using a kit comprised of a plastic bag, tubing, and rectal end-piece. The reactions always occurred with the first use of new kits. A third child developed a systemic reaction with only the rectal end-piece in situ and without infusion of fluid. An in-hospital challenge using a new end-piece in one patient, who was clinically the most sensitive, produced an acute anaphylactoid reaction implicating the end-piece as the most likely source of the problem. The definitive mechanism(s) of the reactions and the agent(s) responsible for them presently remain unknown.

Drug intelligence & clinical pharmacy

This nonblinded, crossover study was undertaken to compare the extent and duration of analgesia a... more This nonblinded, crossover study was undertaken to compare the extent and duration of analgesia after administration of benzydamine 0.15% oral rinse and Hospital for Sick Children (HSC) mouthwash for pain (nystatin 7000 U/ml, lidocaine viscous 0.58 ml/ml in NaCl 0.9%) in pediatric patients with antineoplastic-induced stomatitis. Each mouthwash was administered as a paint or a gargle q2h while the child was awake on two consecutive days. Patients older than three years were asked to describe their pain by means of a pictorial or a visual analog scale. Pain was assessed by the investigator, parent, or nurse caring for the patient as well as the patient whenever possible before each dose and 10, 30, and 60 minutes after the first three doses each day for four days. Stomatitis severity was graded daily. Four patients completed the study protocol; an additional three patients dropped out of the study due to severe stinging when benzydamine oral rinse was administered. The case histories of the patients who completed the study are presented. Both preparations reduced pain for at least one hour in most instances but not for two hours. Three of four patients elected to continue treatment with HSC mouthwash for pain. Study recruitment was halted due to the ethical concern of continuing with the knowledge that benzydamine oral rinse causes oral pain and stinging, especially in patients with severe stomatitis.

American journal of hospital pharmacy

A targeted drug review of cefuroxime use in pediatric patients is described. Because of a 65% inc... more A targeted drug review of cefuroxime use in pediatric patients is described. Because of a 65% increase in cefuroxime costs over one year, pharmacists assessed the appropriateness of cefuroxime therapy from October 13 to December 20, 1987. This assessment was done within 48 hours after the prescription was written and again after 72 hours of cefuroxime therapy, when bacteriology and susceptibility data were available. When a drug order was inappropriate, a pharmacist intervened with the prescribing physician. For comparison, data collection forms were completed for patients who had received cefuroxime before and after the study period. Before the study period, 42% of the cefuroxime orders were inappropriate with respect to dosage or indication at the time of the initial order; this rate fell to 26% during the study period and increased to 33% after the study period. After 72 hours of therapy, the rates of inappropriate prescribing were 48% (before study period), 32% (during study period), and 40% (after study period). During the study period, pharmacists intervened in only half of the 51 cefuroxime orders initially deemed to be inappropriate, and only 26% of these interventions resulted in an order change. Although pharmacists met with some success in increasing the appropriateness of cefuroxime prescribing, both pharmacists and physicians resumed their previous monitoring and prescribing habits after the study period had ended.

DICP: the annals of pharmacotherapy

American Journal of Health-System Pharmacy

Journal of Medical Internet Research

Pain is one of the most common and distressing symptoms reported by adolescents with cancer. Desp... more Pain is one of the most common and distressing symptoms reported by adolescents with cancer. Despite advancements in pain assessment and management research, pain due to cancer and/or its treatments continues to be poorly managed. Our research group has developed a native iPhone application (app) called Pain Squad to tackle the problem of poorly managed pain in the adolescent with cancer group. The app functions as an electronic pain diary and is unique in its ability to collect data on pain intensity, duration, location, and the impact pain has on an adolescent's life (ie, relationships, school work, sleep, mood). It also evaluates medications and other physical and psychological pain management strategies used. Users are prompted twice daily at configurable times to complete 20 questions characterizing their pain and the app transmits results to a database for aggregate reporting through a Web interface. Each diary entry represents a pain case filed by an adolescent with cance...

Pediatric Drugs, 2010

Existing guidelines for the prevention of antineoplastic chemotherapy-induced nausea and vomiting... more Existing guidelines for the prevention of antineoplastic chemotherapy-induced nausea and vomiting (CINV) in children are constrained by the lack of robust evidence. Current guidelines recommend the use of a serotonin 5-HT(3) receptor antagonist plus a corticosteroid to prevent acute CINV. Consequently, antiemetic agents that are recommended for use in adult cancer patients do not appear in the current pediatric guidelines. In addition, there is no information to guide the selection of alternative antiemetic agents for children who either cannot receive the recommended agents or who do not respond adequately to the treatment. Possible barriers to adherence to the pediatric antiemetic selection guidelines that are currently available are discussed, and published pediatric experience with antiemetic agents recommended in the current adult antiemetic selection guidelines (dolasetron, tropisetron, palonosetron, aprepitant) is summarized in this review. The use of novel and emerging antiemetic therapeutic interventions {metopimazine, diphenhydramine (Benadryl)-lorazepam (Avitan)-dexamethasone (Decadron) [BAD], nabilone, acupuncture, midazolam, olanzapine, mirtazapine, gabapentin, droperidol} in children are explored.

Journal of the American Academy of Dermatology, 1985