A new method for assessment of drug disposition in muscle: application of statistical moment theory to local perfusion systems.

A new experimental system is used to determine exact information concerning local drug disposition. Rabbit hind leg is perfused in situ using a single-pass technique, and outflow curves of drugs are analyzed using statistical moment theory. By the introduction of chromatographic concepts and the application of the well-stirred model to the local perfusion system, physiologically and/or physicochemically meaningful parameters are derived from the first three moments. Moreover, in the assessment, drug disposition is divided into elimination and distribution. The elimination process is also evaluated with respect to rate and extent. This system is used to elucidate the disposition characteristics of mitomycin C and its lipophilic derivative nonyloxycarbonyl mitomycin C.