F. Pelsor, L. Allen, P. Creaven
Aug 1, 1978
Citations
1
Influential Citations
23
Citations
Quality indicators
Journal
Journal of pharmaceutical sciences
Abstract
The formation and elimination of the metabolite of 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-beta-D-glucopyranoside) (I) were studied in seven patients with advanced cancer who received I intravenously. The plasma concentration-time data best fit a triexponential equation. The volume of the metabolite compartment (27.5 liters) was calculated as a fraction of the extrapolated volume. A larger body clearance (111.7 ml/min) of metabolite as compared to the renal clearance (31.3 ml/min) indicates that the metabolite is lost from the plasma equivalent space by another elimination route. The combination of metabolite data presented here with previously published data for unchanged I leads to a multicompartment model for the distribution, metabolism, and excretion of I and its metabolite. A comparison of algebraically derived model transfer constants with those evaluated by computer fitting the system of differential equations is presented.