Publication: Pharmacokinetic and pharmacodynamic assessment of co-amoxiclav in the treatment of melioidosis
Issued Date
2006-12-01
Resource Type
ISSN
14602091
03057453
03057453
Other identifier(s)
2-s2.0-33845357081
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Antimicrobial Chemotherapy. Vol.58, No.6 (2006), 1215-1220
Suggested Citation
Wirongrong Chierakul, Jinda Wangboonskul, Thida Singtoroj, Wirichada Pongtavornpinyo, Jennifer M. Short, Bina Maharjan, Vanaporn Wuthiekanun, David A B Dance, Prapit Teparrukkul, Niklas Lindegardh, Sharon J. Peacock, Nicholas P. Day, Wipada Chaowagul, Nicholas J. White Pharmacokinetic and pharmacodynamic assessment of co-amoxiclav in the treatment of melioidosis. Journal of Antimicrobial Chemotherapy. Vol.58, No.6 (2006), 1215-1220. doi:10.1093/jac/dkl389 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/23283
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Title
Pharmacokinetic and pharmacodynamic assessment of co-amoxiclav in the treatment of melioidosis
Abstract
Objectives: We conducted a prospective pharmacokinetic study of oral co-amoxiclav in patients with melioidosis to determine the optimal dosage and dosing interval in this potentially fatal infection. Patients and methods: Serial plasma concentrations were measured after administration of two 1 g tablets of Augmentin® (1750 mg of amoxicillin and 250 mg of clavulanate) to 14 adult patients with melioidosis. Monte Carlo simulation was used to predict the concentration of each drug following multiple doses of co-amoxiclav at different dosages and dose intervals. The proportion of the dose-interval above MIC (T > MIC) was calculated from 10 000 simulated subject plasma concentration profiles together with chequerboard MIC data from 46 clinical isolates and four reference strains of Burkholderia pseudomallei. Results: The median (range) observed maximum plasma concentrations of amoxicillin and clavulanate were 11.5 (3.3-40.2) mg/L and 5.1 (0.8-12.1) mg/L, respectively. The median (range) elimination half-lives were 94 (73-215) and 89 (57-140) min, respectively. Simulation indicated that co-amoxiclav 1750/250 mg given at 4, 6, 8 or 12 hourly dosing intervals would be associated with a T > MIC of ≤50% in 0.7%, 2.8%, 8.6% and 33.2% of patients, respectively. Corresponding proportions for T > MIC of ≥90% were 95.8%, 78.6%, 50.2% and 10.8%, respectively. Conclusions: The dosing interval for co-amoxiclav (750/250 mg) in melioidosis should not be greater than 6 h. © 2006 Oxford University Press.