Multicompartment pharmacokinetic model of 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-beta-D-glucopyranoside) in humans.

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.

• Authors: F R Pelsor, L M Allen, P J Creaven
• Journal: Journal of pharmaceutical sciences (J Pharm Sci) Vol. 67 Issue 8 Pg. 1106-8 (Aug 1978) ISSN: 0022-3549 [Print] United States
• PMID: 671246 (Publication Type: Journal Article)

Chemical References

• Etoposide
• Podophyllotoxin

Topics

• Etoposide (metabolism)
• Humans
• Kinetics
• Models, Biological
• Podophyllotoxin (analogs & derivatives)