Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya
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Date
2003-07Author
Thomson, AH
Kokwaro, GO
Muchohi, SN
English, M
Mohammed, S
Edwards, G
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
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Samples were withdrawn 1 h after a single i.m. injection of 8 mg x kg(-1) gentamicin and the next morning prior to any further dosing.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.
URI
http://www.ncbi.nlm.nih.gov/pubmed/12848772http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/28927
Citation
Br J Clin Pharmacol. 2003 Jul;56(1):25-31Publisher
University of Nairobi. Department of Pharmaceutics & Pharmacy Practice, Faculty of Pharmacy, College of Health Sciences
Collections
- Faculty of Health Sciences (FHS) [10377]