Publication: Pooled population pharmacokinetic analysis of tribendimidine for the treatment of opisthorchis viverrini infections
Issued Date
2019-04-01
Resource Type
ISSN
10986596
00664804
00664804
Other identifier(s)
2-s2.0-85063681163
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.63, No.4 (2019)
Suggested Citation
Isabel Meister, Piyanan Assawasuwannakit, Fiona Vanobberghen, Melissa A. Penny, Peter Odermatt, Somphou Sayasone, Jörg Huwyler, Joel Tarning, Jennifer Keiser Pooled population pharmacokinetic analysis of tribendimidine for the treatment of opisthorchis viverrini infections. Antimicrobial Agents and Chemotherapy. Vol.63, No.4 (2019). doi:10.1128/AAC.01391-18 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/51775
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Pooled population pharmacokinetic analysis of tribendimidine for the treatment of opisthorchis viverrini infections
Abstract
Copyright © 2019 Meister et al. Opisthorchiasis, caused by the foodborne trematode Opisthorchis viverrini, affects more than 8 million people in Southeast Asia. In the framework of a phase 2b clinical trial conducted in Lao People’s Democratic Republic, pharmacokinetic samples were obtained from 125 adult and adolescent O. viverrini-infected patients treated with 400 mg tribendimidine following the design of a sparse sampling scheme at 20 min and 2, 7.75, 8, and 30 h after treatment using dried blood spot sampling. Pharmacokinetic data for the metabolites deacetylated amidantel (dADT) and acetylated dADT (adADT) were pooled with data from two previous ascending-dose trials and evaluated using nonlinear mixed-effects modeling. The observed pharmacokinetic data were described using a flexible transit absorption model for the active metabolite dADT, followed by one-compartment disposition models for both metabolites. Significant covariates were age, body weight, formulation, and breaking of the enteric coating on the tablets. There were significant associations between O. viverrini cure and both the dADT maximum concentration and the area under the concentration-time curve (P 0.001), with younger age being associated with a higher probability of cure. Modeling and simulation of exposures in patients with different weight and age combinations showed that an oral single dose of 400 mg tribendimidine attained therapeutic success in over 90% of adult patients. Our data confirmed that tribendimidine could be a valuable novel alternative to the standard treatment, praziquantel, for the treatment of O. viverrini infections.