2004
DOI: 10.1007/s00280-004-0873-3 View full text |Buy / Rent full text
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Abstract: Poor absorption may be playing a greater role than extensive first-pass metabolism in the incomplete oral bioavailability of BMS-387032 seen in rats. The efflux transporter, P-glycoprotein, may be responsible for limiting absorption, as BMS-387032 appears to be a substrate of P-glycoprotein.

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“…Interestingly, flavopiridol has recently been shown to be transported by mouse Abcb1 [38], [39]. Similarly, higher levels of SNS-032 have been detected in brains of Abcb1 knockout mice than in wild type mice, suggesting that SNS-032 is a substrate of mouse P-glycoprotein [40]. We believe these discrepancies may be due to interspecies differences, in accordance with observations recently reviewed by Chu et al [41].…”
Section: Discussionsupporting
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“…Interestingly, flavopiridol has recently been shown to be transported by mouse Abcb1 [38], [39]. Similarly, higher levels of SNS-032 have been detected in brains of Abcb1 knockout mice than in wild type mice, suggesting that SNS-032 is a substrate of mouse P-glycoprotein [40]. We believe these discrepancies may be due to interspecies differences, in accordance with observations recently reviewed by Chu et al [41].…”
Section: Discussionsupporting
“…The antiproliferative activity of the compound was not affected by P-glycoprotein overexpression and resulted in nearly identical IC 50 values in genetically matched drug-sensitive and drugresistant cells. In contrast, BMS-387032 has been reported to act as a substrate of P-glycoprotein (41).…”
Section: Discussionmentioning
“…When the same computational model was applied to 25 structurally diverse compounds whose rat biliary excretion data were published by different laboratories (Hirom et al, 1972b;Russell and Klaassen 1973;Fahrig et al, 1989;Monsarrat et al, 1990;Masuda et al, 1997;Hinchman et al, 1998;Payan et al, 1999;Song et al, 1999;Arimori et al, 2003;Chong et al, 2003;Funakoshi et al, 2003;Moriwaki et al, 2003;Kamath et al, 2005aKamath et al, ,b, 2008Kurihara et al, 2005;Takayanagi et al, 2005;Akashi et al, 2006;Beconi et al, 2007), the predicted and observed biliary excretion values were again very close for most compounds. The clear exceptions were cephradine and paclitaxel (Monsarrat et al, 1990;Moriwaki et al, 2003).…”
Section: Luo Et Almentioning