JAC Advance Access published online on September 26, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl389
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
* To whom correspondence should be addressed. 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 Conclusions: The dosing interval for co-amoxiclav (750/250 mg) in melioidosis should not be greater than 6 h.
Received March 16, 2006
Revised August 24, 2006
Accepted August 31, 2006
Original article
Pharmacokinetic and pharmacodynamic assessment of co-amoxiclav in the treatment of melioidosis
Wirongrong Chierakul 1 *, Jinda Wangboonskul 2, Thida Singtoroj 3, Wirichada Pongtavornpinyo 3, Jennifer M. Short 4, Bina Maharjan 3, Vanaporn Wuthiekanun 3, David A. B. Dance 5, Prapit Teparrukkul 6, Niklas Lindegardh 4, Sharon J. Peacock 4, Nicholas P. Day 4, Wipada Chaowagul 6, and Nicholas J. White 4
2 Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand
3 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
4 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK
5 Health Protection Agency (South West), Tamar Science Park, 1 Davy Road, Plymouth, Devon PL6 8BX, UK
6 Medical Department, Sappasithiprasong Hospital, Ubon Ratchathani, Thailand
Wirongrong Chierakul, E-mail: tmwcr{at}mahidol.ac.th
Abstract 
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. C. Cheng, E. S. McBryde, V. Wuthiekanun, W. Chierakul, P. Amornchai, N. P. J. Day, N. J. White, and S. J. Peacock Dosing Regimens of Cotrimoxazole (Trimethoprim-Sulfamethoxazole) for Melioidosis Antimicrob. Agents Chemother., October 1, 2009; 53(10): 4193 - 4199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Cheng, W. Chierakul, W. Chaowagul, P. Chetchotisakd, D. Limmathurotsakul, D. A. B. Dance, S. J. Peacock, and B. J. Currie Consensus Guidelines for Dosing of Amoxicillin-Clavulanate in Melioidosis Am J Trop Med Hyg, February 1, 2008; 78(2): 208 - 209. [Abstract] [Full Text] [PDF]
|
|