A Systematic Review and Meta-analysis of Isoniazid Pharmacokinetics in Healthy Volunteers and Patients with Tuberculosis |
| |
| Affiliation: | 1. College of Pharmacy, University of Iowa, Iowa City, IA, USA;2. Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USA;3. Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA;4. Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia;1. Eli Lilly and Company, Lilly Diabetes, Indianapolis, IN, USA;2. HealthCore, Inc, Wilmington, DE, USA;1. Junior Resident, Department of Pharmacology, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India;2. Professor, Department of Pharmacology, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India;3. Director Professor, Department of Pediatrics, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India;4. Director Professor, Department of Biochemistry, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India;5. Head, Department of Chest Clinic, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India;1. Department of Global Health, University of Washington, Seattle, WA, USA;2. Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA;3. University of Bordeaux, Bordeaux, France;4. MRC Clinical Trials Unit, University College London, London, UK;5. University Félix Houphouet-Boigny, Abidjan, Côte d’Ivoire;6. Wellcome Centre for Infectious Disease Research in Africa, University of Cape Town, Cape Town, South Africa;7. Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa;8. School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa;9. Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa;10. The Francis Crick Institute, London, UK;11. Department of Infectious Diseases, Imperial College London, London, UK;12. School of Medicine, Center for Tuberculosis Research, Johns Hopkins University, Baltimore, MD, USA;13. South African Centre for Epidemiological Modelling and Analysis, Stellenbosch, South Africa;1. Laboratory of Pharmacology, Faculty of Medicine, University of Monastir, 5019 Monatir, Tunisie;2. Unit of Chronobiology, Foundation A.-de-Rothschild, 75940 Paris, France;3. Laboratory of Biomonitoring of the Environment (LR01/ES14), Faculty of Science Bizerta, University of Carthage, 7021 Bizerta, Tunisie;1. The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China;2. Clinical Research Center for Phase I, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China;3. The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, PR China;4. Department of Infectious Diseases, Fujian Medical University, Fuzhou, 350025, PR China;5. Drug Clinical Study Center for Phase I, Wuxi People''s Hospital, Wuxi, 214023, PR China;1. Department of Pharmacy, College of Pharmacy, Yonsei University, Incheon, Republic of Korea;2. Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Republic of Korea;3. Department of Pharmaceutical Medicine and Regulatory Science, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, Republic of Korea;4. College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea;5. College of Pharmacy, Yeungnam University, Gyeongsangbuk-do, Republic of Korea;6. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea;7. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-Si, Gyeonggi-Do, Republic of Korea;8. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea |
| |
| Abstract: | PurposeThis systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis (TB), evaluates whether the current INH dose regimen is appropriate in patients with TB, and evaluates the impact of N-acetyl-transferase-2 (NAT2) status on the PK properties of INH.MethodsA systematic approach was conducted to find studies with relevant INH PK data published in the English language up to February 2018. The PK properties of INH were extracted with their respective INH dosages and were dose normalized to allow a fair comparison between healthy volunteers and patients with TB. Meta-analysis was then performed for the Cmax and AUC estimates for all INH dosages.FindingsNinety studies were included in this systematic review. TB status significantly affected the INH Cmax and AUC estimates. In healthy volunteers, the dose-normalized INH Cmax and AUC were statistically higher than those of patients with TB. No significant differences were found in dose-normalized Cmax and AUC between adults with TB and adults with TB/HIV; however, the AUC in pediatric patients was significantly different between patients with TB and patients with TB/HIV. In addition, no significance was observed comparing the dose-normalized Cmax and AUC of pediatric patients with TB and TB/HIV with their respective adult counterparts. Dose-normalized INH Cmax and AUC in patients with fast and intermediate NAT2 were significantly lower than in patients with slow NAT2.ImplicationsThe current recommended dosages of INH were found to produce less drug exposure in patients with TB when compared with healthy volunteers. NAT2 polymorphism greatly impacts the PK properties of INH; hence, testing for acetylator status is highly recommended, and therapeutic drug monitoring would help reduce INH toxicity. |
| |
| Keywords: | isoniazid meta-analysis pharmacokinetics systemic review tuberculosis |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
