Pharmacokinetic approach for optimizing gentamicin use in neonates during the first week of life (original) (raw)
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Once-daily gentamicin dosing of 4 Mg/Kg/dose in neonates
Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2005
Since gentamicin is one of the most commonly prescribed antibiotics for culture-proven or suspected sepsis in neonates, interest has increased in refining dosing regimens for improved efficacy and decreased toxicity. Usually, 2.5 mg gentamicin/kg is infused twice daily, but its large volume of distribution, slow renal clearance and concentration-dependent character, suggests longer dosing intervals would be more appropriate. From a previous study, 22% of neonates who received a once-daily gentamicin dosage of 5 mg/kg/day had unacceptably high trough levels (i.e. > 2 microg/mL). The authors studied 105 neonates (of > or = 34 wk gestational age or > or = 2, 000 g body weight) admitted to the Neonatal Unit, Srinagarind Hospital, Khon Kaen University; at risk, or with clinical features of sepsis, receiving a once-daily gentamicin dosing of 4 mg/kg intravenously. Peak (i.e. efficacy) and trough (i.e. toxicity) serum gentamicin concentrations were collected on day 3 of therapy. O...
Clinical pharmacokinetics in optimal gentamicin dosing regimen in neonates
Central European Journal of Medicine, 2014
Gentamicin is readily used for suspected or proven sepsis in neonates, yet it shows considerable inter-individual pharmacokinetic variability, which limits achievements of therapeutic levels. Hence, the aim of this study was to compare peak and trough gentamicin concentrations according to dosing regimen, to evaluate pharmacokinetic parameters, and to consider adjustments of dosing regimen. Babies with infection were treated with 1 h infusion, and daily dose of 5 or 7.5 mg/kg depending on the age. Patients were randomized into two groups: I — dosing interval 12 h (n=8), II — 24 h (n=11). Two steady-state blood samples were obtained. Pharmacokinetic parameters were calculated using one-compartment model. The results showed a difference (p<0.05) in peak gentamicin concentrations between the groups, and tendency of lower trough levels in the group II. Calculated pharmacokinetic parameters included the volume of distribution (Vd) 0.52±0.47 l/kg, clearance (CL) 0.055±0.036 l/hkg and a...
Pharmacokinetic basis for the use of extended interval dosage regimens of gentamicin in neonates
Journal of Antimicrobial Chemotherapy, 2004
Objectives: To analyse the pharmacokinetic basis for the use of extended-interval dosage regimens of gentamicin in neonates using population pharmacokinetics. Patients and methods: The population pharmacokinetics of gentamicin was studied retrospectively in a population of 113 neonates divided into two groups: one for computing the population model (n 5 97) and another for validation (n 5 36). A one-compartment pharmacokinetic model and non-linear mixed-effects modelling were used to assess the population pharmacokinetic model. Results: Weight (W) and postnatal age (PA) were the covariates that influenced the pharmacokinetic parameters of gentamicin. The final population model obtained was: distribution volume, V (L) 5 0.636 3 W (kg) 0.852 ; clearance, Cl (L/h) 5 0.032 3 W (kg) 1.482 1 0.0024 3 PA (days). The predictive performance of the model in the population validation was adequate for clinical purposes. The optimized population model allowed us to simulate gentamicin serum levels and their variability, in this kind of patient, when extended-interval dosage administration regimens were implemented. Conclusions: According to our pharmacokinetic population model, initial doses of gentamicin of 10 mg/kg, and dosage intervals between 36-48 h, appear to be appropriate to achieve target peak and trough serum levels of 15-20 and <0.5 mg/L, respectively, when extended-interval dosage regimens are implemented in newborns. The half-life of gentamicin in premature babies of very low weight and gestational age <31 weeks is long. Thus, to achieve serum concentrations in the 1-10 mg/L range, the use of dosage regimens of 5 mg/kg at 36-48 h dosage intervals seems suitable.
Pharmacotherapy, 2009
To determine the pharmacokinetic outcomes of a simplified, weight-based, extended-interval gentamicin dosing protocol for critically ill neonates. Design. Retrospective medical record review with pharmacokinetic analysis. Setting. Two neonatal intensive care units in a pediatric tertiary care system. Patients. Sequential sample of 644 critically ill neonates less than 7 days old without evidence of renal dysfunction who received gentamicin, dosed by using a simplified, weight-based, extended-interval dosing protocol, on the first day of life for suspected sepsis between February 2003 and January 2008, and who had subsequent gentamicin plasma concentrations measured during their first week of life. Measurements and Main Results. Data were collected on birth weight, gestational age at birth, serum creatinine concentration during the first 10 days of life, medical conditions, and concomitant drugs. Gentamicin dosing and its pharmacokinetic parameters were noted for each patient. A mean dose of 3.96 mg/kg/dose of gentamicin was administered intravenously every 48 hours in neonates weighing less than 1250 g at birth and every 24 hours in those weighing 1250 g or more. If the neonate received concurrent indomethacin, however, gentamicin was given every 48 hours. Protocol success was defined as a peak gentamicin plasma concentration of 7-10 mg/L and a trough concentration less than 2 mg/L. Mean gentamicin peak and trough concentrations were 9.38 mg/L (95% confidence interval [CI] 9.24-9.52 mg/L) and 1.00 mg/L (95% CI 0.96-1.04 mg/L), respectively. With use of the protocol, 361 neonates (56.1%) achieved gentamicin peak plasma concentrations in the range defined as successful and 610 neonates (94.7%) achieved successful trough concentrations. The mean gentamicin apparent volume of distribution and half-life were 0.48 L/kg (95% CI 0.47-0.49 L/kg) and 8.31 hours (95% CI 8.09-8.52 hrs), respectively. Conclusion. This simplified, weight-based, extended-interval gentamicin dosing protocol for critically ill neonates was effective in achieving therapeutic peak plasma concentrations of gentamicin in most of the patients and, as a high proportion of patients had acceptable trough concentrations, may minimize the potential for toxicity.
An extended interval dosing method for gentamicin in neonates
Journal of Antimicrobial Chemotherapy, 2001
Traditional gentamicin dosing every 8-24 h depending on age and weight in neonates does not provide the ideal concentration-time profile to both optimize the concentration- dependent killing by aminoglycosides and minimize toxicity. Fifty-three neonates were audited prospectively while receiving gentamicin 2.5 mg/kg every 8-24 h, aiming for peak concentra- tions (Cmax) of 6-10 mg/L and trough concentrations (Cmin) <2 mg/L.
Once daily dose gentamicin in neonates - is our dosing correct?
Acta Paediatrica, 2009
The aim of this paper is to study the safety and efficacy (measured by therapeutic level) of once daily gentamicin in neonates &amp;gt;or=32 weeks of gestation and &amp;lt;or=7 days of age. Level II neonatal intensive care unit. Neonates &amp;gt;or=32 weeks of gestation and &amp;lt;or=7 days of age treated with gentamicin for presumed sepsis. Gentamicin was administered by intravenous injection at 4 mg/kg/day once daily. Peak and trough gentamicin levels were measured at the third dose. In neonates with gestational age between 32 and 36 weeks, 14 out of 65 (22%) had trough serum concentration &amp;gt;2 mg/L. Only 39 (60%) had peak and trough levels within the therapeutic range. All babies who had audiometric evaluation (62 out of 65) had normal hearing. Out of the 65 babies, 60 had paired serum creatinine levels estimated and none had evidence of renal dysfunction. Among term neonates, only 2 out of 50 had the trough serum concentration of &amp;gt;2 mg/L. In 38 (76%) of the 50 neonates, the trough serum gentamicin concentration was &amp;lt;2.0 mg/L and the peak level was &amp;lt;10 mg/L. Forty-eight babies had audiometric evaluation which was normal. A dose of 4 mg/kg/day produces serum gentamicin levels outside the therapeutic range in two-fifths of neonates between 32 and 36 +/- 6 weeks. A single dose of 4 mg/kg/day of gentamicin is appropriate for term babies and probably excessive for 32-36 weeks&amp;#39; neonates.
Pharmacokinetics of once-daily dosing of gentamicin in neonates
The Journal of Pediatrics, 1997
In a prospective, randomized trial of once-daily versus twice-daily intravenous or intramuscular dosing with gentamicin, 11 neonates received 5.0 mg/kg once daily and 15 received 2.5 mg/kg twice daily for 2 ro 3 days. The once-daily intravenous dosing group and the twice-daily intravenous or intramuscular dosing group, respectively, had mean steady-state gentamicin peak concentrations of 10.7 versus 6.6 micrograms/ml (p < 0.05), 6-hour postdosing concentrations of 4.7 versus 2.8 micrograms/ml (p < 0.05), trough concentrations of 1.7 versus 1.7 micrograms/ml, elimination half-life of 8.8 versus 5.4 hours (p < 0.05), and volume of distribution at steady state of 0.67 versus 0.46 L/kg. No nephrotoxic effects were identified in any group. Once-daily gentamicin therapy with 5.0 mg/kg in neonates achieves peak serum levels that are more suitable for optimal bacterial killing than those which traditional regimens achieve. Similar trough levels suggest that even larger doses and longer dosing intervals may be ideal in term neonates.
The Kinetic Profile of Gentamicin in Premature Neonates
Journal of Pharmacy and Pharmacology, 2000
The kinetic pro®le of gentamicin in premature infants has been studied to enable the development of optimized dosage schedules for neonatal intensive-care units and to stress the relationship between the pharmacokinetic parameters and several demographic, developmental and clinical factors which might be associated with changes in gentamicin disposition.
Gulhane Medical Journal, 2022
Aims: Gentamicin is routinely used in neonates as an empirical antibiotic for suspected sepsis at a dose of 4.0 mg/kg, either 24 or 36 hourly based on premenstrual age. Regularly, therapeutic drug monitoring is performed. This study was conducted to determine gentamicin blood level in one-week-of-life neonates on 4 mg/kg treatment. Methods: Neonates who received gentamicin in a special care nursery ward were identified from the records retrospectively. The included subjects were neonates between 3 and 7 days old treated with gentamicin for at least three days. Admission diagnoses, dosing protocol (including dosage, the timing of the doses, and timing of blood samples) and measured gentamicin trough and peak levels were recorded. Results: A total of 290 neonates met the inclusion criteria (male: 57.6%). Over 30% of the subjects treated with gentamicin experienced potential toxicity with trough levels above 1.0 μg/mL, and 15.9% of them had sub efficacy of the drug (peak level below 5 μg/mL). Six neonates had trough levels above 2.0 μg/mL. The percentage of potential toxicity was higher in subjects with presumed sepsis, in those with bodyweight between 2.5-2.99 kg and with 24hour dosing interval. Conclusions: We propose a trough-only monitoring protocol in non-critically ill neonates, as the practice of monitoring pre and post often necessitate additional blood sampling. The decision of not determining the peak levels routinely can be based on the outcome that gentamicin dosage of 4.0 mg/kg likely provides peak levels in desired range without any added risk of toxicity.