Comparative bioavailability of clofazimine coevaporate in the pig

Abstract

The systemic availability of a solid dispersion (coevaporate) of clofazimine (CLF) in poly(vinyl methyl ether maleic anhydride) copolymer (PVM/MA) was tested in the pig. Single 100 mg oral doses of the coevaporate and the commercial product, Lamprene (Ciba-Geigy) were administered on separate occasions (separated by a two-week washout period) to four pigs (two males, two females) in a random cross-over study. Multiple plasma samples, obtained from an indwelling jugular-vein cannula, following drug administration, were analysed by an HPLC method for CLF. Pharmacokinetic analyses of the plasma CLF concentration-time data were performed. A paired t-test indicated significant differences (p < 0.05) between the coevaporate and Lamprene in the Cpmax, tmax, and AUC. The calculated relative systemic bioavailability (Frel) of CLF from the coevaporate, relative to that from Lamprene, was three. It is concluded that formulation of CLF, as a solid dispersion, may provide enhanced aqueous dissolution and systemic absorption and may also provide high therapeutic blood levels. These could lead to reduction in the current therapeutic doses and, consequently, minimization of drug-related side effects.