American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2020
Comment Randomized Controlled Trial Multicenter StudyRecommended Reading from Boston University School of Medicine Fellows.
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Am. J. Respir. Crit. Care Med. · Sep 2020
Rifapentine Population Pharmacokinetics and Dosing Recommendations for Latent Tuberculosis Infection.
Rationale: Rifapentine has been investigated at various doses, frequencies, and dosing algorithms, but clarity on the optimal dosing approach is lacking. Objectives: To characterize rifapentine population pharmacokinetics, including autoinduction, and determine optimal dosing strategies for short-course rifapentine-based regimens for latent tuberculosis infection. Methods: Rifapentine pharmacokinetic studies were identified though a systematic review of literature. ⋯ Pharmacokinetic simulations showed that current weight-based dosing leads to lower exposures in individuals with low weight, which can be overcome with flat dosing. In HIV-positive patients, 30% higher doses are required to match drug exposure in HIV-negative patients. Conclusions: Weight-based dosing of rifapentine should be removed from clinical guidelines, and higher doses for HIV-positive patients should be considered to provide equivalent efficacy.