Editor-in-Chief Hatice Kübra Elçioğlu Vice Editors Levent Kabasakal Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Journal of Research in Pharmacy 2022 , Vol 26 , Issue 6
Therapeutic Drug Monitoring in Pediatric Patients Treated with Anti-Tuberculosis Medications by High Performance Liquid Chromatography
Betul OKUYAN1,Fatih TOK2,Sevgi KARAKUŞ2,Nazan DALGIÇ3,Erkan ÇAKIR4,Levent MIDYAT5,Bedia KOÇYİĞİT-KAYMAKÇIOĞLU2,Ufuk Eren BERK4,Fikret Vehbi İZZETTIN6,Sevim ROLLAS2,Mesut SANCAR1
1Department of Clinical Pharmacy, Faculty of Pharmacy, Marmara University, Başıbüyük 34854, Istanbul, Türkiye
2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Başıbüyük 34854, Istanbul, Türkiye
3Division of Pediatric Infectious Diseases, University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, Sarıyer 34453, Istanbul, Türkiye
4Department of Pediatrics, Faculty of Medicine, Bezmialem Vakif University, Fatih 34093, Istanbul, Türkiye
5Division of Pediatric Pulmonology, Sureyyapasa Chest Diseases and Thoracic Surgery Teaching Hospital, Maltepe 34844, Istanbul, Türkiye
6Department of Clinical Pharmacy, Faculty of Pharmacy, Bezmialem Vakif University, Fatih 34093, Istanbul, Türkiye
DOI : 10.29228/jrp.281 The aim of this study is to perform therapeutic drug monitoring for isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA) in pediatric tuberculosis patients. The study was carried out in 3 different training-research hospitals in Istanbul, Türkiye between 2011 and 2012. The pediatric patients (aged ≤14 years) who initiated the standard primary anti-tuberculosis therapy were included in this study. The serum samples were collected 3 hours after the first medication doses were given on the 5th day of treatment. Chromatographic experiments were performed on an Agilent 1100 High-Performance Liquid Chromatography (HPLC) system, and the separation was carried out on a Nova-Pak C18 (3.9x150 mm, 5 μm, Merck) analytical column. In this HPLC method, the gradient elusion delivered 3% to 40% (v/v) acetonitrile in phosphate buffer was used, and diode array detector. Twenty-three children (60.9% male) patients were included with a mean age of 111.70 ± 59.94 months. Plasma levels were measured sub-therapeutically for INH in 14, RIF in 10, and PZA in 5 patients, according to the normal range of adult patients. Maximum plasma concentrations after three hours were found between 0.53-14.02 mg/L for INH, 11.17-60.39 mg/L for PZA, 2.15-16.75 mg/L for RIF. In conclusion, this method has been successfully applied to simultaneously determine RIF, INH, and PZA plasma levels in pediatric tuberculosis patients. RIF and INH plasma levels were found to be lower in pediatric patients with tuberculosis compared to target range of adult patients. Keywords : HPLC; tuberculosis; pediatric patients; therapeutic drug monitoring
Marmara University