Ken Ilett - Academia.edu (original) (raw)

Papers by Ken Ilett

Antimicrobial Agents and Chemotherapy, 2012

Artemisinin-naphthoquine (ART-NQ) is a fixed-dose coformulated antimalarial therapy recommended a... more Artemisinin-naphthoquine (ART-NQ) is a fixed-dose coformulated antimalarial therapy recommended as a single-dose treatment and marketed in Papua New Guinea among other tropical countries. We conducted a tolerability, safety, and efficacy study of ART-NQ for Papua New Guinean children aged 5 to 12 years with uncomplicated malaria, comparing single-dose ART-NQ (15 and 6 mg/kg of body weight) given with water (group 1; n = 15), single-dose ART-NQ (22 and 9 mg/kg) given with milk (group 2; n = 17), or two daily doses of 22 and 9 mg/kg given with water (group 3; n = 16). Of the 48 children (45 with Plasmodium falciparum malaria, 2 with Plasmodium vivax malaria, and 1 with mixed-species malaria), 2 in group 2 did not attend all follow-up assessments. All regimens were well tolerated, with no serious adverse events. There were no clinically significant changes in pulse, blood pressure, rate-corrected electrocardiographic QT, routine biochemistry/hematology, or hearing after treatment. Feve...

11th International …, 2011

Methods: A survey of therapeutic drug monitoring (TDM) practices in Australasia was undertaken in... more Methods: A survey of therapeutic drug monitoring (TDM) practices in Australasia was undertaken in late 2007 with 57 responses received. 42% described the responding institution as a hospital, 11% as a hospital pathology provider and 47% as pathology ...

Drug Metabolism and Disposition, 2002

The aim of this study was to elucidate the metabolic pathways for dihydroartemisinin (DHA), the a... more The aim of this study was to elucidate the metabolic pathways for dihydroartemisinin (DHA), the active metabolite of the artemisinin derivative artesunate (ARTS). Urine was collected from 17 Vietnamese adults with falciparum malaria who had received 120 mg of ARTS i.v., and metabolites were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Human liver microsomes were incubated with [12-3 H]DHA and cofactors for either glucuronidation or cytochrome P450-catalyzed oxidation. Human liver cytosol was incubated with cofactor for sulfation. Metabolites were detected by HPLC-MS and/or HPLC with radiochemical detection. Metabolism of DHA by recombinant human UDP-glucuronosyltransferases (UGTs) was studied. HPLC-MS analysis of urine identified ␣-DHA-␤-glucuronide (␣-DHA-G) and a product characterized as the tetrahydrofuran isomer of ␣-DHA-G. DHA was present only in very small amounts. The ratio of the tetrahydrofuran isomer, ␣-DHA-G, was highly variable (median 0.75; range 0.09-64). Nevertheless, ␣-DHA-G was generally the major urinary product of DHA glucuronidation in patients. The tetrahydrofuran isomer appeared to be at least partly a product of nonenzymic reactions occurring in urine and was readily formed from ␣-DHA-G by iron-mediated isomerization. In human liver microsomal incubations, DHA-G (diastereomer unspecified) was the only metabolite found (V max 177 ؎ 47 pmol min ؊1 mg ؊1 , K m 90 ؎ 16 M). ␣-DHA-G was formed in incubations of DHA with expressed UGT1A9 (K m 32 M, V max 8.9 pmol min ؊1 mg ؊1) or UGT2B7 (K m 438 M, V max 10.9 pmol mg ؊1 min ؊1) but not with UGT1A1 or UGT1A6. There was no significant metabolism of DHA by cytochrome-P450 oxidation or by cytosolic sulfotransferases. We conclude that ␣-DHA-G is an important metabolite of DHA in humans and that its formation is catalyzed by UGT1A9 and UGT2B7.

11th International …, 2011

Methods: A survey of therapeutic drug monitoring (TDM) practices in Australasia was undertaken in... more Methods: A survey of therapeutic drug monitoring (TDM) practices in Australasia was undertaken in late 2007 with 57 responses received. 42% described the responding institution as a hospital, 11% as a hospital pathology provider and 47% as pathology ...

Schizophrenia Research, 1998

aggressive behaviour (from 59% to 24%) and the use of concomitant medication.

The Medical Journal of Australia, 2013

A working party (WP) from the Australasian Association of Clinical Biochemists, Australasian Soci... more A working party (WP) from the Australasian Association of Clinical Biochemists, Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, Royal College of Pathologists of Australasia and Royal Australasian College of Physicians recommends the following: *mass units should be used for reporting therapeutic drug concentrations in Australia and New Zealand; and the litre (L) should be used as the denominator when expressing concentration. Examples of these units are mg/L and μg/L Exceptions to these principles include: *drugs for which there is current uniformity of reporting and supporting information using molar units, notably lithium (mmol/L) and methotrexate (μmol/L); *drugs that are also present as endogenous substances, where the units used routinely should continue to be used. This applies to many substances, including minerals (eg, iron; μmol/L), vitamins (eg, vitamin D; nmol/L) and hormones (eg, thyroxine; pmol/L). *drugs for which the denominator is not a 198 of fluid and there is international uniformity of reporting (eg, thiopurine metabolites; per 109 red blood cells). These recommendations relate to drugs that are used therapeutically, whether measured for therapeutic drug monitoring purposes or for assessment of overdose. Other substances, such as drugs of misuse, heavy metals or environmental toxins, were not considered by the WP and are thus not covered by this document. These recommendations should also be applied to other supporting documentation such as published guidelines, journal articles and websites. The implementation of these recommendations in New Zealand is subject to local confirmation.

Objective. To evaluate the stability and tolerability of high concentrations of bupivacaine-opioi... more Objective. To evaluate the stability and tolerability of high concentrations of bupivacaine-opioid solutions when used by intrathecal infusion.

Antimicrobial Agents and Chemotherapy, 2012

Artemisinin-naphthoquine (ART-NQ) is a fixed-dose coformulated antimalarial therapy recommended a... more Artemisinin-naphthoquine (ART-NQ) is a fixed-dose coformulated antimalarial therapy recommended as a single-dose treatment and marketed in Papua New Guinea among other tropical countries. We conducted a tolerability, safety, and efficacy study of ART-NQ for Papua New Guinean children aged 5 to 12 years with uncomplicated malaria, comparing single-dose ART-NQ (15 and 6 mg/kg of body weight) given with water (group 1; n = 15), single-dose ART-NQ (22 and 9 mg/kg) given with milk (group 2; n = 17), or two daily doses of 22 and 9 mg/kg given with water (group 3; n = 16). Of the 48 children (45 with Plasmodium falciparum malaria, 2 with Plasmodium vivax malaria, and 1 with mixed-species malaria), 2 in group 2 did not attend all follow-up assessments. All regimens were well tolerated, with no serious adverse events. There were no clinically significant changes in pulse, blood pressure, rate-corrected electrocardiographic QT, routine biochemistry/hematology, or hearing after treatment. Feve...

11th International …, 2011

Methods: A survey of therapeutic drug monitoring (TDM) practices in Australasia was undertaken in... more Methods: A survey of therapeutic drug monitoring (TDM) practices in Australasia was undertaken in late 2007 with 57 responses received. 42% described the responding institution as a hospital, 11% as a hospital pathology provider and 47% as pathology ...

Drug Metabolism and Disposition, 2002

The aim of this study was to elucidate the metabolic pathways for dihydroartemisinin (DHA), the a... more The aim of this study was to elucidate the metabolic pathways for dihydroartemisinin (DHA), the active metabolite of the artemisinin derivative artesunate (ARTS). Urine was collected from 17 Vietnamese adults with falciparum malaria who had received 120 mg of ARTS i.v., and metabolites were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Human liver microsomes were incubated with [12-3 H]DHA and cofactors for either glucuronidation or cytochrome P450-catalyzed oxidation. Human liver cytosol was incubated with cofactor for sulfation. Metabolites were detected by HPLC-MS and/or HPLC with radiochemical detection. Metabolism of DHA by recombinant human UDP-glucuronosyltransferases (UGTs) was studied. HPLC-MS analysis of urine identified ␣-DHA-␤-glucuronide (␣-DHA-G) and a product characterized as the tetrahydrofuran isomer of ␣-DHA-G. DHA was present only in very small amounts. The ratio of the tetrahydrofuran isomer, ␣-DHA-G, was highly variable (median 0.75; range 0.09-64). Nevertheless, ␣-DHA-G was generally the major urinary product of DHA glucuronidation in patients. The tetrahydrofuran isomer appeared to be at least partly a product of nonenzymic reactions occurring in urine and was readily formed from ␣-DHA-G by iron-mediated isomerization. In human liver microsomal incubations, DHA-G (diastereomer unspecified) was the only metabolite found (V max 177 ؎ 47 pmol min ؊1 mg ؊1 , K m 90 ؎ 16 M). ␣-DHA-G was formed in incubations of DHA with expressed UGT1A9 (K m 32 M, V max 8.9 pmol min ؊1 mg ؊1) or UGT2B7 (K m 438 M, V max 10.9 pmol mg ؊1 min ؊1) but not with UGT1A1 or UGT1A6. There was no significant metabolism of DHA by cytochrome-P450 oxidation or by cytosolic sulfotransferases. We conclude that ␣-DHA-G is an important metabolite of DHA in humans and that its formation is catalyzed by UGT1A9 and UGT2B7.

11th International …, 2011

Methods: A survey of therapeutic drug monitoring (TDM) practices in Australasia was undertaken in... more Methods: A survey of therapeutic drug monitoring (TDM) practices in Australasia was undertaken in late 2007 with 57 responses received. 42% described the responding institution as a hospital, 11% as a hospital pathology provider and 47% as pathology ...

Schizophrenia Research, 1998

aggressive behaviour (from 59% to 24%) and the use of concomitant medication.

The Medical Journal of Australia, 2013

A working party (WP) from the Australasian Association of Clinical Biochemists, Australasian Soci... more A working party (WP) from the Australasian Association of Clinical Biochemists, Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, Royal College of Pathologists of Australasia and Royal Australasian College of Physicians recommends the following: *mass units should be used for reporting therapeutic drug concentrations in Australia and New Zealand; and the litre (L) should be used as the denominator when expressing concentration. Examples of these units are mg/L and μg/L Exceptions to these principles include: *drugs for which there is current uniformity of reporting and supporting information using molar units, notably lithium (mmol/L) and methotrexate (μmol/L); *drugs that are also present as endogenous substances, where the units used routinely should continue to be used. This applies to many substances, including minerals (eg, iron; μmol/L), vitamins (eg, vitamin D; nmol/L) and hormones (eg, thyroxine; pmol/L). *drugs for which the denominator is not a 198 of fluid and there is international uniformity of reporting (eg, thiopurine metabolites; per 109 red blood cells). These recommendations relate to drugs that are used therapeutically, whether measured for therapeutic drug monitoring purposes or for assessment of overdose. Other substances, such as drugs of misuse, heavy metals or environmental toxins, were not considered by the WP and are thus not covered by this document. These recommendations should also be applied to other supporting documentation such as published guidelines, journal articles and websites. The implementation of these recommendations in New Zealand is subject to local confirmation.

Objective. To evaluate the stability and tolerability of high concentrations of bupivacaine-opioi... more Objective. To evaluate the stability and tolerability of high concentrations of bupivacaine-opioid solutions when used by intrathecal infusion.