OBJECTIVE: To study the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in adult tuberculosis (TB) patients and examine factors that influence drug pharmacokinetics. METHODS: Adult TB patients (n = 101) receiving thrice-weekly anti-tuberculosis treatment in the Revised National TB Control Programme (RNTCP) were studied. The study was conducted at steady state after directly observed drug administration. RMP, INH and PZA concentrations were estimated using high-performance liquid chromatography and NAT2 genotyping by real-time polymerase chain reaction. RESULTS: RMP peak concentration (Cmax) was sub-therapeutic (<8 μg/ml) in 88% of the patients. The Cmax of RMP, INH and PZA at 2 h was observed in respectively 83.2%, 97.0% and 92.1% of the patients. The Cmax and area under the curve from 0 to 8 h (AUC0-8) of PZA was lower in TB patients with diabetes mellitus than in non-diabetics. Significant associations were observed between the Cmax and the AUC0-8 of RMP, INH and PZA with drug doses; RMP with category of treatment; INH with smoking, body mass index and N-acetyl transferase 2 genotype; and PZA with sex and smoking. CONCLUSIONS: Several risk factors for drug concentration variations were identified. Two-hour post-dosing drug concentrations mimicked Cmax. A high proportion of TB patients had RMP Cmax below the expected range, which is a matter of concern.
OBJECTIVE: To study the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in adult tuberculosis (TB) patients and examine factors that influence drug pharmacokinetics. METHODS: Adult TB patients (n = 101) receiving thrice-weekly anti-tuberculosis treatment in the Revised National TB Control Programme (RNTCP) were studied. The study was conducted at steady state after directly observed drug administration. RMP, INH and PZA concentrations were estimated using high-performance liquid chromatography and NAT2 genotyping by real-time polymerase chain reaction. RESULTS:RMP peak concentration (Cmax) was sub-therapeutic (<8 μg/ml) in 88% of the patients. The Cmax of RMP, INH and PZA at 2 h was observed in respectively 83.2%, 97.0% and 92.1% of the patients. The Cmax and area under the curve from 0 to 8 h (AUC0-8) of PZA was lower in TB patients with diabetes mellitus than in non-diabetics. Significant associations were observed between the Cmax and the AUC0-8 of RMP, INH and PZA with drug doses; RMP with category of treatment; INH with smoking, body mass index and N-acetyl transferase 2 genotype; and PZA with sex and smoking. CONCLUSIONS: Several risk factors for drug concentration variations were identified. Two-hour post-dosing drug concentrations mimicked Cmax. A high proportion of TB patients had RMP Cmax below the expected range, which is a matter of concern.
Authors: Rob C van Wijk; Wanbin Hu; Sharka M Dijkema; Dirk-Jan van den Berg; Jeremy Liu; Rida Bahi; Fons J Verbeek; Ulrika S H Simonsson; Herman P Spaink; Piet H van der Graaf; Elke H J Krekels Journal: Br J Pharmacol Date: 2020-11-03 Impact factor: 8.739
Authors: A K Hemanth Kumar; V Chandrasekaran; T Kannan; A Lakshmi Murali; J Lavanya; V Sudha; Soumya Swaminathan; Geetha Ramachandran Journal: Eur J Clin Pharmacol Date: 2016-09-20 Impact factor: 2.953
Authors: Prakruti S Rao; Christopher C Moore; Amir A Mbonde; Edwin Nuwagira; Patrick Orikiriza; Dan Nyehangane; Mohammad H Al-Shaer; Charles A Peloquin; Jean Gratz; Suporn Pholwat; Rinah Arinaitwe; Yap Boum; Juliet Mwanga-Amumpaire; Eric R Houpt; Leonid Kagan; Scott K Heysell; Conrad Muzoora Journal: Antibiotics (Basel) Date: 2021-06-18
Authors: Benjamin Guiastrennec; Geetha Ramachandran; Mats O Karlsson; A K Hemanth Kumar; Perumal Kannabiran Bhavani; N Poorana Gangadevi; Soumya Swaminathan; Amita Gupta; Kelly E Dooley; Radojka M Savic Journal: Clin Pharmacol Ther Date: 2018-02-02 Impact factor: 6.875