Pharmacokinetic Evidence from the HIRIF Trial To Support Increased Doses of Rifampin for Tuberculosis

• Published in: Antimicrobial agents and chemotherapy Vol. 61; no. 8
• Main Authors: Peloquin, C A, Velásquez, G E, Lecca, L, Calderón, R I, Coit, J, Milstein, M, Osso, E, Jimenez, J, Tintaya, K, Sanchez Garavito, E, Vargas Vasquez, D, Mitnick, C D, Davies, G
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.08.2017
• Subjects: Administration, Oral; Adolescent; Adult; Antitubercular Agents; Antitubercular Agents - administration & dosage; Antitubercular Agents - pharmacokinetics; Dose-Response Relationship, Drug; Female; Humans; Male; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Peru; Pharmacology; Rifampin; Rifampin - administration & dosage; Rifampin - pharmacokinetics; Tuberculosis; Tuberculosis - drug therapy; Tuberculosis - microbiology; Young Adult; pharmacokinetics; antitubercular agents; rifampin; tuberculosis
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.00038-17

Rifamycins exhibit concentration-dependent killing of ; higher exposures potentially induce better outcomes. We randomized 180 tuberculosis patients in Peru to receive rifampin at 10, 15, or 20 mg/kg/day. A total of 168 had noncompartmental pharmacokinetic analyses; 67% were sampled twice, and 33% were sampled six times. The doses administered were well tolerated. The median area under the concentration-time curve from 0 to 6 h (interquartile range) was 24.9 (17.6 to 32.1), 43.1 (30.3 to 57.5), or 55.5 (35.7 to 73.2) h · μg/ml. The median maximum drug concentration in serum in the experimental arms reached the target of 8 μg/ml. Continued investigation of higher rifampin doses is warranted. (This study has been registered at ClinicalTrials.gov under registration no. NCT01408914.).