Multicompartment pharmacokinetic model of 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-beta-D-glucopyranoside) in humans. 1978

F R Pelsor, and L M Allen, and P J Creaven

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.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D011034 Podophyllotoxin A lignan (LIGNANS) found in PODOPHYLLIN resin from the roots of PODOPHYLLUM plants. It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. Epipodophyllotoxin,CPH86,Condyline,Condylox,Podocon-25,Podofilm,Podofilox,Podophyllotoxin, (5R-(5 alpha,5a alpha,8a alpha,9 alpha))-Isomer,Podophyllotoxin, (5R-(5 alpha,5a alpha,8a alpha,9 beta))-Isomer,Podophyllotoxin, (5R-(5 alpha,5a alpha,8a beta,9 alpha))-Isomer,Podophyllotoxin, (5R-(5 alpha,5a beta,8a alpha,9 beta))-Isomer,Wartec,Warticon
D005047 Etoposide A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. Demethyl Epipodophyllotoxin Ethylidine Glucoside,Celltop,Eposide,Eposin,Eto-GRY,Etomedac,Etopos,Etoposide Pierre Fabre,Etoposide Teva,Etoposide, (5S)-Isomer,Etoposide, (5a alpha)-Isomer,Etoposide, (5a alpha,9 alpha)-Isomer,Etoposide, alpha-D-Glucopyranosyl Isomer,Etoposido Ferrer Farma,Exitop,Lastet,NSC-141540,Onkoposid,Riboposid,Toposar,VP 16-213,VP-16,Vepesid,Vépéside-Sandoz,Eto GRY,Etoposide, alpha D Glucopyranosyl Isomer,NSC 141540,NSC141540,Teva, Etoposide,VP 16,VP 16 213,VP 16213,VP16,Vépéside Sandoz,alpha-D-Glucopyranosyl Isomer Etoposide
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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F R Pelsor, and L M Allen, and P J Creaven
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