Pharmacokinetics and animal studies of rifapentine in tuberculosis

Rifapentine (RPT) is a long-acting rifamycin derivative which has a much lo nger half-life in mice and in humans than rifampicin (RIF). The minimal inh ibitory concentration (MIC) of RPT against Mycobacterium tuberculosis is si milar or slightly lower than that of RIF. The pharmacokinetics of rifapenti ne have been explored in both humans and mice and provided results more fav orable for an intermittent treatment of tuberculosis than RIF and rifabutin (RBT). The activity of RPT against M. tuberculosis was better than that of RIF and RBT and was dose-related in both preventine and curative murine mo dels of tuberculosis. RPT treatment administered once weekly was effective against M. tuberculosis but not when administered once every 2 or 3 weeks. An RPT-containing regimen was as effective as the daily standard regimen in the initial phase of treatment if it was preceded by 2 weeks of daily trea tment containing RIF, isoniazid (INH), pyrazinamide (PZA) and streptomycin (SM) followed by a once-weekly regimen of RPT, INH, PZA and SM for 6 weeks. RPT is a highly promising drug for intermittent therapy of tuberculosis. ( C) 1999 Prous Science. All rights reserved.