ABCMdb

PMID: 18509645

O'Bryant CL, Lieu CH, Leong S, Boinpally R, Basche M, Gore L, Leonardi K, Schultz MK, Hariharan S, Chow L, Diab S, Gibbs A, Eckhardt SG
A dose-ranging study of the pharmacokinetics and pharmacodynamics of the selective apoptotic antineoplastic drug (SAAND), OSI-461, in patients with advanced cancer, in the fasted and fed state.
Cancer Chemother Pharmacol. 2009 Feb;63(3):477-89. Epub 2008 May 29., [PubMed]

Sentences

No. Mutations Sentence Comment

273 ABCG2 p.Gln141Lys ABCG2 p.Val12Met A mutation results in markedly decreased protein expression, and low level drug resistance, as compared to wild-type BRCP c For ABCG-2 #34 the of the A mutation frequency in Caucasians is 4.7%; and for ABCG-2 #421 the A mutation frequency in Caucasians is 25.9% Pt # ABCG-2 #34a ABCG-2 #421b Racec Val12 Met mutation Sequencing result Gln141 Lys mutation Sequencing result 01015 No Wild-type: G/G No Wild-type: C/C White 01016 No Wild-type: G/G Yes Heterozygote: C/A White 01017 Yes Homozygote: A/A No Wild-type: C/C Asian 01018 No Wild-type: G/G Yes Heterozygote: C/A White 01019 No Wild-type: G/G No Wild-type: C/C White 01020 Yes Heterozygote: A/G No Wild-type: C/C White 01021 No Wild-type: G/G Yes Heterozygote: C/A White 01022 No Wild-type: G/G No Wild-type: C/C Black 01023 No Wild-type: G/G Yes Heterozygote: C/A White 01024 No Wild-type: G/G No Wild-type: C/C White 01026 No Wild-type: G/G No Wild-type: C/C White 01027 No Wild-type: G/G No Wild-type: C/C White 01028 No Wild-type: G/G No Wild-type: C/C White 01029 No Wild-type: G/G No Wild-type: C/C White 01031 No Wild-type: G/G Yes Homozygote: A/A White 01032 No Wild-type: G/G No Wild-type: C/C White 01033 No Wild-type: G/G No Wild-type: C/C White A prior study of OSI-461 demonstrated that Cmax and AUC values increased in an approximate linear fashion as the dose was increased from 100 to 400 mg BID with a signiWcant amount of interpatient variability [35]. Login to comment