Pooled population pharmacokinetic analysis of tribendimidine for the treatment of Opisthorchis viverrini infections
Opisthorchiasis, caused by the food-borne trematode Opisthorchis viverrini, affects more than 8 million people in Southeast Asia. In the framework of a phase 2b clinical trial conducted in Lao PDR, pharmacokinetic samples from 125 adult and adolescent O. viverrini patients treated with 400 mg triben...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Microbiology
2019
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| _version_ | 1797106166137880576 |
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| author | Meister, I Assawasuwannakit, P Vanobberghen, F Penny, M Odermatt, P Sayasone, S Huwyler, J Tarning, J Keiser, J |
| author_facet | Meister, I Assawasuwannakit, P Vanobberghen, F Penny, M Odermatt, P Sayasone, S Huwyler, J Tarning, J Keiser, J |
| author_sort | Meister, I |
| collection | OXFORD |
| description | Opisthorchiasis, caused by the food-borne trematode Opisthorchis viverrini, affects more than 8 million people in Southeast Asia. In the framework of a phase 2b clinical trial conducted in Lao PDR, pharmacokinetic samples from 125 adult and adolescent O. viverrini patients treated with 400 mg tribendimidine were obtained following the design of an sparse sampling scheme at 20 min, 2, 7.75, 8 and 30 h after treatment, using dried blood spot sampling. Pharmacokinetic data for the metabolites dADT and adADT were pooled with data from two previous dose-ascending trials and evaluated using nonlinear mixed-effects modelling. 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 dADT Cmax and AUC (p-values <0.001), with younger age associated with a higher probability of cure. Modelling and simulation of exposures in a 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. |
| first_indexed | 2024-03-07T06:57:52Z |
| format | Journal article |
| id | oxford-uuid:febeda71-c766-4c2f-aec2-e57343b4a3a2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:57:52Z |
| publishDate | 2019 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:febeda71-c766-4c2f-aec2-e57343b4a3a22022-03-27T13:39:01ZPooled population pharmacokinetic analysis of tribendimidine for the treatment of Opisthorchis viverrini infectionsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:febeda71-c766-4c2f-aec2-e57343b4a3a2EnglishSymplectic Elements at OxfordAmerican Society for Microbiology2019Meister, IAssawasuwannakit, PVanobberghen, FPenny, MOdermatt, PSayasone, SHuwyler, JTarning, JKeiser, JOpisthorchiasis, caused by the food-borne trematode Opisthorchis viverrini, affects more than 8 million people in Southeast Asia. In the framework of a phase 2b clinical trial conducted in Lao PDR, pharmacokinetic samples from 125 adult and adolescent O. viverrini patients treated with 400 mg tribendimidine were obtained following the design of an sparse sampling scheme at 20 min, 2, 7.75, 8 and 30 h after treatment, using dried blood spot sampling. Pharmacokinetic data for the metabolites dADT and adADT were pooled with data from two previous dose-ascending trials and evaluated using nonlinear mixed-effects modelling. 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 dADT Cmax and AUC (p-values <0.001), with younger age associated with a higher probability of cure. Modelling and simulation of exposures in a 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. |
| spellingShingle | Meister, I Assawasuwannakit, P Vanobberghen, F Penny, M Odermatt, P Sayasone, S Huwyler, J Tarning, J Keiser, J Pooled population pharmacokinetic analysis of tribendimidine for the treatment of Opisthorchis viverrini infections |
| title | Pooled population pharmacokinetic analysis of tribendimidine for the treatment of Opisthorchis viverrini infections |
| title_full | Pooled population pharmacokinetic analysis of tribendimidine for the treatment of Opisthorchis viverrini infections |
| title_fullStr | Pooled population pharmacokinetic analysis of tribendimidine for the treatment of Opisthorchis viverrini infections |
| title_full_unstemmed | Pooled population pharmacokinetic analysis of tribendimidine for the treatment of Opisthorchis viverrini infections |
| title_short | Pooled population pharmacokinetic analysis of tribendimidine for the treatment of Opisthorchis viverrini infections |
| title_sort | pooled population pharmacokinetic analysis of tribendimidine for the treatment of opisthorchis viverrini infections |
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