Population pharmacokinetics of ivermectin after mass drug administration in lymphatic filariasis endemic communities of Tanzania
Abstract Ivermectin (IVM) is a drug of choice used with albendazole for mass drug administration (MDA) to halt transmission of lymphatic filariasis. We investigated IVM pharmacokinetic (PK) variability for its dose optimization during MDA. PK samples were collected at 0, 2, 4, and 6 h from individua...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.13038 |
| _version_ | 1797388946724880384 |
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| author | Adam M. Fimbo Eulambius M. Mlugu Eliford Ngaimisi Kitabi Gerald S. Kulwa Mohammed A. Iwodyah Rajabu Hussein Mnkugwe Peter P. Kunambi Alpha Malishee Appolinary A. R. Kamuhabwa Omary M. Minzi Eleni Aklillu |
| author_facet | Adam M. Fimbo Eulambius M. Mlugu Eliford Ngaimisi Kitabi Gerald S. Kulwa Mohammed A. Iwodyah Rajabu Hussein Mnkugwe Peter P. Kunambi Alpha Malishee Appolinary A. R. Kamuhabwa Omary M. Minzi Eleni Aklillu |
| author_sort | Adam M. Fimbo |
| collection | DOAJ |
| description | Abstract Ivermectin (IVM) is a drug of choice used with albendazole for mass drug administration (MDA) to halt transmission of lymphatic filariasis. We investigated IVM pharmacokinetic (PK) variability for its dose optimization during MDA. PK samples were collected at 0, 2, 4, and 6 h from individuals weighing greater than 15 kg (n = 468) receiving IVM (3‐, 6‐, 9‐, or 12 mg) and ALB (400 mg) during an MDA campaign in Tanzania. Individual characteristics, including demographics, laboratory/clinical parameters, and pharmacogenetic variations were assessed. IVM plasma concentrations were quantified by liquid‐chromatography tandem mass spectrometry and analyzed using population‐(PopPK) modeling. A two‐compartment model with transit absorption kinetics, and allometrically scaled oral clearance (CL/F) and central volume (Vc/F) was adapted. Fitting of the model to the data identified 48% higher bioavailability for the 3 mg dose compared to higher doses and identified a subpopulation with 97% higher mean transit time (MTT). The final estimates for CL/F, Vc/F, intercompartment clearance, peripheral volume, MTT, and absorption rate constant for a 70 kg person (on dose other than 3 mg) were 7.7 L/h, 147 L, 20.4 L/h, 207 L, 1.5 h, and 0.71/h, respectively. Monte‐Carlo simulations indicated that weight‐based dosing provides comparable exposure across weight bands, but height‐based dosing with capping IVM dose at 12 mg for individuals with height greater than 160 cm underdoses those weighing greater than 70 kg. Variability in IVM PKs is partly explained by body weight and dose. The established PopPK model can be used for IVM dose optimization. Height‐based pole dosing results in varying IVM exposure in different weight bands, hence using weighing scales for IVM dosing during MDA is recommended. |
| first_indexed | 2024-03-08T22:48:20Z |
| format | Article |
| id | doaj.art-8eb56a80061b4c679a9f5a5480a7eaf8 |
| institution | Directory Open Access Journal |
| issn | 2163-8306 |
| language | English |
| last_indexed | 2024-03-08T22:48:20Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | CPT: Pharmacometrics & Systems Pharmacology |
| spelling | doaj.art-8eb56a80061b4c679a9f5a5480a7eaf82023-12-16T18:59:25ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062023-12-0112121884189610.1002/psp4.13038Population pharmacokinetics of ivermectin after mass drug administration in lymphatic filariasis endemic communities of TanzaniaAdam M. Fimbo0Eulambius M. Mlugu1Eliford Ngaimisi Kitabi2Gerald S. Kulwa3Mohammed A. Iwodyah4Rajabu Hussein Mnkugwe5Peter P. Kunambi6Alpha Malishee7Appolinary A. R. Kamuhabwa8Omary M. Minzi9Eleni Aklillu10Department of Global Public Health Karolinska Institutet, Karolinska University Hospital Stockholm SwedenDepartment of Pharmaceutics and Pharmacy Practice, School of Pharmacy Muhimbili University of Health and Allied Sciences Dar es Salaam TanzaniaDivision of Pharmacometrics Office of Clinical Pharmacology, US Food and Drug Administration Silver Spring Maryland USATanzania Medicines and Medical Devices Authority (TMDA) Dar es Salaam TanzaniaTanzania Medicines and Medical Devices Authority (TMDA) Dar es Salaam TanzaniaDepartment of Clinical Pharmacology, School of Biomedical Sciences, Campus College of Medicine Muhimbili University of Health and Allied Sciences Dar es Salaam TanzaniaDepartment of Clinical Pharmacology, School of Biomedical Sciences, Campus College of Medicine Muhimbili University of Health and Allied Sciences Dar es Salaam TanzaniaNational Institute for Medical Research, Tanga Center Tanga TanzaniaDepartment of Clinical Pharmacy and Pharmacology, School of Pharmacy Muhimbili University of Health and Allied Sciences Dar es Salaam TanzaniaDepartment of Clinical Pharmacy and Pharmacology, School of Pharmacy Muhimbili University of Health and Allied Sciences Dar es Salaam TanzaniaDepartment of Global Public Health Karolinska Institutet, Karolinska University Hospital Stockholm SwedenAbstract Ivermectin (IVM) is a drug of choice used with albendazole for mass drug administration (MDA) to halt transmission of lymphatic filariasis. We investigated IVM pharmacokinetic (PK) variability for its dose optimization during MDA. PK samples were collected at 0, 2, 4, and 6 h from individuals weighing greater than 15 kg (n = 468) receiving IVM (3‐, 6‐, 9‐, or 12 mg) and ALB (400 mg) during an MDA campaign in Tanzania. Individual characteristics, including demographics, laboratory/clinical parameters, and pharmacogenetic variations were assessed. IVM plasma concentrations were quantified by liquid‐chromatography tandem mass spectrometry and analyzed using population‐(PopPK) modeling. A two‐compartment model with transit absorption kinetics, and allometrically scaled oral clearance (CL/F) and central volume (Vc/F) was adapted. Fitting of the model to the data identified 48% higher bioavailability for the 3 mg dose compared to higher doses and identified a subpopulation with 97% higher mean transit time (MTT). The final estimates for CL/F, Vc/F, intercompartment clearance, peripheral volume, MTT, and absorption rate constant for a 70 kg person (on dose other than 3 mg) were 7.7 L/h, 147 L, 20.4 L/h, 207 L, 1.5 h, and 0.71/h, respectively. Monte‐Carlo simulations indicated that weight‐based dosing provides comparable exposure across weight bands, but height‐based dosing with capping IVM dose at 12 mg for individuals with height greater than 160 cm underdoses those weighing greater than 70 kg. Variability in IVM PKs is partly explained by body weight and dose. The established PopPK model can be used for IVM dose optimization. Height‐based pole dosing results in varying IVM exposure in different weight bands, hence using weighing scales for IVM dosing during MDA is recommended.https://doi.org/10.1002/psp4.13038 |
| spellingShingle | Adam M. Fimbo Eulambius M. Mlugu Eliford Ngaimisi Kitabi Gerald S. Kulwa Mohammed A. Iwodyah Rajabu Hussein Mnkugwe Peter P. Kunambi Alpha Malishee Appolinary A. R. Kamuhabwa Omary M. Minzi Eleni Aklillu Population pharmacokinetics of ivermectin after mass drug administration in lymphatic filariasis endemic communities of Tanzania CPT: Pharmacometrics & Systems Pharmacology |
| title | Population pharmacokinetics of ivermectin after mass drug administration in lymphatic filariasis endemic communities of Tanzania |
| title_full | Population pharmacokinetics of ivermectin after mass drug administration in lymphatic filariasis endemic communities of Tanzania |
| title_fullStr | Population pharmacokinetics of ivermectin after mass drug administration in lymphatic filariasis endemic communities of Tanzania |
| title_full_unstemmed | Population pharmacokinetics of ivermectin after mass drug administration in lymphatic filariasis endemic communities of Tanzania |
| title_short | Population pharmacokinetics of ivermectin after mass drug administration in lymphatic filariasis endemic communities of Tanzania |
| title_sort | population pharmacokinetics of ivermectin after mass drug administration in lymphatic filariasis endemic communities of tanzania |
| url | https://doi.org/10.1002/psp4.13038 |
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