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Interaction of Docetaxel ("Taxotere") with Human P-glycoprotein

Overview
Specialty Oncology
Date 2000 Feb 9
PMID 10665657
Citations 25
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Abstract

The interaction of docetaxel ("Taxotere") with P-glycoprotein (P-gp) was examined using porcine kidney epithelial LLC-PK1 and LLC-GA5-COL150 cells, overexpressing human P-gp selectively on the apical plasma membrane by transfection of human MDR1 cDNA into the LLC-PK1 cells. The basal-to-apical transport of [14C]docetaxel in LLC-GA5-COL150 cells significantly exceeded that in LLC-PK1 cells, but the apical-to-basal transport was decreased in LLC-GA5-COL150 cells. The intracellular accumulation after its basal or apical application to LLC-GA5-COL150 cells was 4- to 20-fold lower than that of LLC-PK1 cells. Multidrug resistance (MDR) modulators, i.e., cyclosporin A and SDZ PSC 833, inhibited the basal-to-apical transport and increased the apical-to-basal transport of [14C]docetaxel in LLC-GA5-COL150 cells, but verapamil affected only apical-to-basal transport. The intracellular accumulation after basal or apical application to LLC-GA5-COL150 cells was also increased by these three MDR modulators. These observations demonstrated that docetaxel is a substrate for human P-gp, suggesting that docetaxel-drug interactions occur via P-gp. The inhibition of [14C]docetaxel transport by the MDR modulators, as well as daunorubicin and vinblastine, was also found in LLC-PK1 cells, which endogenously express P-gp at lower levels, and concentrations showing similar levels of inhibition were lower than those in the case of LLC-GA5-COL150 cells. These observations indicate that it is necessary to consider the pharmacokinetic and pharmacodynamic interactions of docetaxel via P-gp.

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References
1.
Tanigawara Y, Okamura N, Hirai M, Yasuhara M, Ueda K, Kioka N . Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1). J Pharmacol Exp Ther. 1992; 263(2):840-5. View

2.
Baggetto L . Biochemical, genetic, and metabolic adaptations of tumor cells that express the typical multidrug-resistance phenotype. Reversion by new therapies. J Bioenerg Biomembr. 1997; 29(4):401-13. DOI: 10.1023/a:1022459100409. View

3.
Takara K, Tanigawara Y, Komada F, Nishiguchi K, Sakaeda T, Okumura K . Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Biol Pharm Bull. 2000; 22(12):1355-9. DOI: 10.1248/bpb.22.1355. View

4.
Clarke S, Rivory L . Clinical pharmacokinetics of docetaxel. Clin Pharmacokinet. 1999; 36(2):99-114. DOI: 10.2165/00003088-199936020-00002. View

5.
Royer I, Monsarrat B, Sonnier M, Wright M, Cresteil T . Metabolism of docetaxel by human cytochromes P450: interactions with paclitaxel and other antineoplastic drugs. Cancer Res. 1996; 56(1):58-65. View