Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya.
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 METHODS: Samples were withdrawn 1 h after a single i.m. injection of 8 mg x kg(-1) gentamicin and the next morning prior to any further dosing.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 d...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2003
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| _version_ | 1797060182637805568 |
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| author | Thomson, A Kokwaro, G Muchohi, SN English, M Mohammed, S Edwards, G |
| author_facet | Thomson, A Kokwaro, G Muchohi, SN English, M Mohammed, S Edwards, G |
| author_sort | Thomson, A |
| collection | OXFORD |
| description | 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 METHODS: Samples were withdrawn 1 h after a single i.m. injection of 8 mg x kg(-1) gentamicin and the next morning prior to any further dosing.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. |
| first_indexed | 2024-03-06T20:13:44Z |
| format | Journal article |
| id | oxford-uuid:2b7001c0-ec38-4915-8f33-5b57201d4a77 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:13:44Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:2b7001c0-ec38-4915-8f33-5b57201d4a772022-03-26T12:30:58ZPopulation pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2b7001c0-ec38-4915-8f33-5b57201d4a77EnglishSymplectic Elements at Oxford2003Thomson, AKokwaro, GMuchohi, SNEnglish, MMohammed, SEdwards, G 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. |
| spellingShingle | Thomson, A Kokwaro, G Muchohi, SN English, M Mohammed, S Edwards, G Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya. |
| title | Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya. |
| title_full | Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya. |
| title_fullStr | Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya. |
| title_full_unstemmed | Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya. |
| title_short | Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya. |
| title_sort | population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in kenya |
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