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Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya

Thomson, A. H., Kokwaro, G. O., Muchohi, S. N., English, M., Mohammed, S. and Edwards, Geoffrey (2003) 'Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya'. British Journal of Clinical Pharmacology, Vol 56, Issue 1, pp. 25-31.

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Abstract

Aims To determine the population pharmacokinetics of intramuscular (i.m.) gentamicin in African infants with suspected severe sepsis. Methods Samples were withdrawn 1 h after a single i.m. injection of 8 mg kg(-1) gentamicin and the next morning prior to any further dosing. Concentration-time data were analysed with the population pharmacokinetic package NONMEM. Data were fitted using a one-compartment model with a log-normal model for interindividual variability and an additive residual error model. The influence of a range of clinical characteristics was tested on the pharmacokinetics of intramuscular gentamicin and the effect of incorporating interindividual variability on bioavailability was examined. Results The data set comprised 107 patients and 203 concentrations. Peak concentrations ranged from 3.0 mg L-1 to 19.8 mg L-1 (median 10.6 mg L-1) and 'next day' samples from 0.3 mg L-1 to 6.2 mg L-1 .The best models were clearance/bioavailability (CL) (L h(-1)) = 0.0913 x weight (kg) x (age (days) + 1)/11)(0.130) and volume of distribution/bioavailability (V) = 2.02 x (1 + 0.277 x (weight -3)). Therefore, an infant with the median weight of 3 kg and age 10 days would have a predicted CL of 0.274 L h(-1) and V of 2.02 L. Interindividual variability in CL was 40% and in V was 42%. This model required a term for covariance between CL and V. When variability in bioavailability was introduced as an alternative model, interindividual variability in CL was 22%, in V 18% and in relative bioavailability 36%. Conclusions Intramuscular administration of 8 mg kg(-1) gentamicin daily to infants gives mean 1 h peak concentration of 10.6 mg L-1 and a trough concentration of less than 2 mg L-1. Wide variability in the peak concentration may reflect variable absorption rate or bioavailability.

Item Type: Article
Subjects: QV Pharmacology > Anti-Bacterial Agents. Tissue Extracts > QV 350.5.G3 Gentamicins
QV Pharmacology > QV 38 Drug action.
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WB Practice of Medicine > Therapeutics > WB 340 Drug Administration
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 240 Bacteremia. Sepsis. Toxemias
WS Pediatrics > Diseases of Children and Adolescents > General Diseases > WS 205 Pediatric emergencies
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1046/j.1365-2125.2003.01819.x
Depositing User: Users 494 not found.
Date Deposited: 22 Jan 2013 16:54
Last Modified: 06 Feb 2018 13:04
URI: http://archive.lstmed.ac.uk/id/eprint/2687

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