Serum concentrations of clarithromycin and rifampicin in pulmonary Mycobacterium avium complex disease: long-term changes due to drug interactions and their association with clinical outcomes

Journal of Pharmaceutical Health Care and Sciences
Hitoshi ShimomuraTakao Aoyama

Abstract

Concomitant use of clarithromycin (CAM) and rifampicin (RFP) for the treatment of pulmonary Mycobacterium avium complex (MAC) disease affects the systemic concentrations of both drugs due to CYP3A4-related interactions. To date, however, there has been no report that investigates the long-term relationship between the drug concentrations, CYP3A4 activity, and clinical outcomes. Our aim was to investigate the time course of the drug levels in long-term treatment of subjects with pulmonary MAC disease, and examine the correlation of these concentrations with CYP3A4 activity and clinical outcomes. Urine and blood samples from nine outpatients with pulmonary MAC disease were collected on days 1, 15, and 29 (for four subjects, sample collections were continued on days 57, 85, 113, 141, 169, 225, 281, 337, and 365). Serum drug concentrations and urinary levels of endogenous cortisol (F) and 6 beta-hydroxycortisol (6βOHF), the metabolite of F by CYP3A4, were measured, and evaluated 6βOHF/F ratio as a CYP3A4 activity marker. In addition, the clinical outcomes of 4 subjects were evaluated based on examination of sputum cultures and chest images. The mean 6βOHF/F ratio increased from 2.63 ± 0.85 (n = 9) on the first day to 6.96 ± 1.35 on...Continue Reading

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Oct 16, 2019·Antimicrobial Agents and Chemotherapy·Seong Mi MoonByung Woo Jhun

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