Pharmacokinetics of standard dose regimens of rifampicin in patients with pulmonary tuberculosis in Pakistan.
BACKGROUND
This clinical study investigated the pharmacokinetics of standard doses of rifampicin (RMP; 450 and 600 mg) in pulmonary tuberculosis (TB) patients in the context of its high sterilizing potential and the increased frequency of multidrug-resistant TB in Pakistan. The objective of this study was to determine the sufficiency or inadequacy of peak plasma levels of RMP in pulmonary TB patients after the administration of standard doses.


METHODS
Twenty adult patients with newly diagnosed pulmonary TB consented to participate in the study. Blood sampling for pharmacokinetic assessment of RMP was done after at least 14 days of regular daily treatment to ensure steady state. Plasma concentrations of RMP were determined by a validated high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection.


RESULTS
The peak plasma concentration of RMP at 2 h was subtherapeutic, i.e. 3.76 ± 1.23 mg/l (range 1.80-6.62), in all of our patients. Out of 20 patients, 13 (65%), had 2-h plasma concentrations below 4 mg/l.


CONCLUSIONS
This study reports evidence of suboptimal RMP concentrations in a small group of Pakistani TB patients and highlights the need for larger clinical studies to identify possible reasons and consequences of low RMP levels in terms of treatment outcomes. Quality control problems in local drug preparations used widely among TB patients in Pakistan need to be addressed as a matter of urgency.
Department of Pharmacology, Army Medical College, National University of Sciences and Technology, Rawalpindi, Pakistan. abidashaheen97@yahoo.com
Abida
A
Shaheen
Muzammil Hasan
MH
Najmi
Waseem
W
Saeed
Zia-Ur-Rehman
ZU
Farooqi
D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D010154:Pakistan; D010949:Plasma / Q000737:chemistry; D012293:Rifampin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
D000995:Antitubercular Agents; D012293:Rifampin