Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya.
OBJECTIVE
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Samples were withdrawn 1 h after a single i.m. injection of 8 mg x kg(-1) gentamicin and the next morning prior to any further dosing.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 x L(-1) to 19.8 mg x L(-1) (median 10.6 mg x L(-1)) and 'next day' samples from 0.3 mg x L(-1) to 6.2 mg x L(-1). The best models were clearance/bioavailability (CL) (L x 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 x 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 x kg(-1) gentamicin daily to infants gives mean 1 h peak concentration of 10.6 mg x L(-1) and a trough concentration of less than 2 mg x L(-1). Wide variability in the peak concentration may reflect variable absorption rate or bioavailability.
Thomson
Alison H
AH
Pharmacy Department, Western Infirmary, North Glasgow University Hospitals NHS Trust, Glasgow G11 6NT, UK. a.h.thomson@clinmed.gla.ac.uk
Kokwaro
Gilbert O
GO
Muchohi
Simon N
SN
English
Michael
M
Mohammed
Shebbe
S
Edwards
Geoffrey
G
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D005839:Gentamicins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007273:Injections, Intramuscular; D018805:Sepsis / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D005839:Gentamicins