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Murine pharmacokinetics of rifapentine delivered as an inhalable dry powder

Chan, JG and Tyne, AS and Pang, A and McLachlan, AJ and Perera, V and Chan, JC and Britton, WJ and Chan, HK and Duke, CC and Young, PM and Traini, D (2014) Murine pharmacokinetics of rifapentine delivered as an inhalable dry powder. International Journal of Antimicrobial Agents.

Abstract

A novel inhalable rifapentine dry powder formulation could improve pulmonary rifapentine concentrations resulting in a significantly shorter time to treat tuberculosis infection. The pharmacokinetics of rifapentine (20mg/kg) in healthy mice was compared following intratracheal (IT) and intraperitoneal (IP) administration. Plasma, bronchoalveolar lavage (BAL) and tissue samples were collected and drug levels were quantified at time points up to 24h. Concentration-time data were analysed using a mixed-effects modelling approach to provide model-based estimates of area under the concentration-time curve from time 0 to infinity (AUC0-infinity). IT delivery had considerably higher peak rifapentine lung and BAL concentrations and associated AUC0-infinity compared with IP delivery. The plasma AUC0-infinity following IT dry powder delivery was ca. four-fold smaller than the value for IP delivery. Inhaled delivery of rifapentine has the potential to selectively enhance therapeutic efficacy at the pulmonary site of infection whilst minimising systemic exposure and related toxicity

Item Type: Article
Additional Information: NIBR author: Perera, V institute: NIBR contributor address:
Date Deposited: 13 Oct 2015 13:11
Last Modified: 13 Oct 2015 13:11
URI: https://oak.novartis.com/id/eprint/24939

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