Open AccessAltered Pharmacokinetics of Vinblastine in Mdr1a P-glycoprotein-Deficient Mice
Author(s) -
Judith van Asperen,
Alfred H. Schinkel,
Jos H. Beijnen,
W. J. Nooijen,
Piet Borst,
Olaf van Tellingen
Publication year - 1996
Publication title -
journal of the national cancer institute
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.797
H-Index - 356
eISSN - 1460-2105
pISSN - 0027-8874
DOI - 10.1093/jnci/88.14.994
Subject(s) - pharmacokinetics , p glycoprotein , pharmacology , vinblastine , cytotoxic t cell , chemistry , bolus (digestion) , biology , medicine , multiple drug resistance , biochemistry , chemotherapy , in vitro , antibiotics
P-glycoprotein (Pgp) is a membrane protein that acts as an extrusion pump for many cytotoxic drugs. Pgp is expressed in normal tissues, and its (over)expression in tumor cells contributes to their drug resistance. Human Pgp is encoded by the MDR1 gene, In mice, two Pgps (encoded by the mdr1a and mdr1b genes) appear to perform the same function as the single human protein. The simultaneous use of cytotoxic drugs and agents that block Pgp function has raised questions of safety, since a blockade of Pgp in normal tissues could alter drug pharmacokinetics and change the spectrum of toxic side effects. Analysis of the consequences of Pgp blockade has been facilitated by the generation of mice with disrupted mdr1a genes [mdr1a(-/-)].