Dose optimization with population pharmacokinetics of ritonavir-boosted lopinavir for Thai people living with HIV with and without active tuberculosis |
| |
| Institution: | 1. PhD''s Degree Program in Pharmacy, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand;2. Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand;3. HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand;4. Center of Excellence in Tuberculosis, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;5. Center of Excellence for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai, Thailand;1. Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan;2. Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Kainan, Japan;3. Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Japan;1. Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai, 980-8578, Japan;2. Division of Risk Assessment, National Institute of Health Sciences, Tonomachi 3-25-26, Kawasaki-ku, Kanagawa, 210-9501, Japan;3. Regulatory Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan;1. Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Tokyo, Japan;2. Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, Sendai, Japan;3. Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan;4. Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan;5. Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan;1. Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, PR China;2. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, Institute for Liver Diseases of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China;3. The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, 230032, PR China;4. Center for Scientific Research of Anhui Medical University, Hefei, 230032, PR China;5. Hefei Kaifan Analytical Technology Co., Ltd., Hefei, 230051, PR China;1. Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai, 980-8578, Japan;2. Division of Risk Assessment, National Institute of Health Sciences, Tonomachi 3-25-26, Kawasaki-ku, Kawasaki, 210-9501, Japan;3. Laboratory of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526 Japan;4. Department of Drug Metabolism and Pharmacokinetics, Nonclinical Research Center, Tokushima Research Institute, Otsuka Pharmaceutical Co, Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima, 771-0192, Japan;1. The Department of Clinical Pharmacology, Faculty of Medicine Jazan University, Saudi Arabia;2. American University of Health Sciences, Signal Hill, CA, USA;3. Ophthalmology, University of California, San Francisco, CA, USA;4. Ophthalmology, NYU Medical Center, NY, USA |
| |
| Abstract: | BackgroundPrior to dolutegravir availability, ritonavir-boosted lopinavir (LPV/r) was an alternative recommendation when first-line drugs could not be used. A high concentration of protease inhibitors was observed in the Thai people living with HIV (PLWH). Thus, dose reduction of LPV/r may be possible. However, the pharmacokinetics and dose optimization of LPV/r have never been investigated. This study aimed to develop a population pharmacokinetic model of LPV/r and provide dosage optimization in Thai PLWH.MethodsLPV and RTV trough concentrations from Thai PLWH were combined with intensive data. The data were analyzed by the nonlinear mixed-effects modeling approach. The influence of RTV concentration on LPV oral clearance (CL/F) was investigated.ResultsRifampicin (RIF) use increased LPV and RTV CL/F by 2.16-fold and 1.99-fold, respectively. The reduced dose of 300/75 and 200/150 mg twice daily provided a comparable percentage of patients achieving LPV target trough concentration to the standard dose for PI-naïve patients. For HIV/TB co-infected patients receiving RIF who could not tolerate the recommended dose, the reduced dose of 600/150 mg twice daily was recommended.ConclusionThe population pharmacokinetic model was developed by integrating the interaction between LPV and RTV. The reduced LPV/r dosage offers sufficient LPV exposure for Thai PLWH. |
| |
| Keywords: | Lopinavir Ritonavir Population pharmacokinetics Thai people living with HIV NONMEM |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
