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Pooled population pharmacokinetic analysis of tribendimidine for the treatment of Opisthorchis viverrini infections

Meister, Isabel and Assawasuwannakit, Piyanan and Vanobberghen, Fiona and Penny, Melissa A. and Odermatt, Peter and Sayasone, Somphou and Huwyler, Jörg and Tarning, Joel and Keiser, Jennifer. (2019) Pooled population pharmacokinetic analysis of tribendimidine for the treatment of Opisthorchis viverrini infections. Antimicrobial agents and chemotherapy, 63 (4). e01391-18.

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Abstract

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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Eco System Health Sciences > Helminths and Health (Odermatt)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Infectious Disease Modelling > Disease and Intervention Dynamics (Penny)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Helminth Drug Development (Keiser)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Medicine > Clinical Research (Reither)
UniBasel Contributors:Meister, Isabel and Vanobberghen, Fiona and Penny, Melissa and Odermatt, Peter and Keiser, Jennifer
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Microbiology
ISSN:0066-4804
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:07 May 2019 07:32
Deposited On:07 May 2019 07:32

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