Pharmacogenetics of tipifarnib (R115777) transport and metabolism in cancer patients View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-08

AUTHORS

Alex Sparreboom, Sharon Marsh, Ron H. J. Mathijssen, Jaap Verweij, Howard L. McLeod

ABSTRACT

The purpose of this study was to perform exploratory relationships between the pharmacokinetics of the farnesyl transferase inhibitor, tipifarnib (R115777, Zarnestra) and allelic variants of genes coding for ATP binding-cassette transporters and drug-metabolizing enzymes. Twenty-eight patients with advanced solid tumors were treated with tipifarnib administered orally at a dose of 200 or 300 mg. Blood samples were collected for pharmacokinetics and genotyping of 10 variants in genes encoding P-glycoprotein (ABCB1), cytochrome P450 isozymes CYP3A4 and CYP3A5, and UDP glucuronosyltransferase isozyme UGT1A1. The homozygous T -allele of ABCB1*8 (1236C > T ) was associated with a trend for a higher area under the curve of tipifarnib as compared to patients with only one or no variant alleles [mean (+/-SD), 5,303 +/- 1,620 ng.h/mL vs. 3,619 +/- 1,275 ng.h/mL; P = 0.047). No statistically significant differences were observed with any other genetic variant ( P > 0.15). Overall, this study indicates that ABCB1 genotype might be correlated with tipifarnib pharmacokinetics, although considerable overlap in exposure measures between genotype groups was observed. More... »

PAGES

285-289

Identifiers

URI

http://scigraph.springernature.com/pub.10.1023/b:drug.0000026254.97350.fe

DOI

http://dx.doi.org/10.1023/b:drug.0000026254.97350.fe

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039729047

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15122075


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