| Research Title |
Effect of Albumin on In Vitro Paclitaxel Kinetics : Prediction of In Vivo Clearance from In Vitro Data |
| Date of Distribution |
15 October 2009 |
| Conference |
| Title of the Conference |
การแพทย์หัวใจประชาชนในภาวะวิกฤตเศรษฐกิจ (People - Centered Health Care in Economic Crisis Era) |
| Organiser |
คณะแพทยศาสตร์ มหาวิทยาลัยขอนแก่น |
| Conference Place |
ณ ห้องบรรยาย 1-4 อาคารเตรียมวิทยาศาสตร์คลินิก คณะแพทยศาสตร์ มหาวิทยาลัยขอนแก่น |
| Province/State |
ขอนแก่น |
| Conference Date |
13 October 2009 |
| To |
16 October 2009 |
| Proceeding Paper |
| Volume |
24 |
| Issue |
4 |
| Page |
92 |
| Editors/edition/publisher |
รศ.ดร. วราภรณ์ เชื้ออินทร์ |
| Abstract |
Background and Objective : Paclitaxel (PAC) is widely used for treatment of malignant tumors. PAC is metabolized by CYP2C8 and CYP3A4 to 6-hydroxypaclitaxel and 3-phenyl-hydroxypaclitaxel, respectively. It has been demonstrated that arachidonic acid is substrate of CYP2C8. Since polyunsaturated fatty acids (PUFAs) are known to be released from the membranes of in vitro enzyme sources during the course of an incubation which are the inhibitors of CYPs resulting in overestimation of in vitro kinetic parameter Km. Consequently, Intrinsic clearance (CLint ) may be under-estimated. The addition of bovine serum albumin (BSA) to incubations improves estimation of in vivo clearance from in vitro kinetic parameters by decreasing Km with a minor effect on maximum velocity (Vmax) for drugs metabolized by CYP2C9. The aims were to investigate the effect of BSA on the kinetics of PAC 6-hydroxylation, demonstrate inhibition of PAC 6-hydroxylation by fatty acid mixture, and investigate the reversal effect of BSA on the inhibition by fatty acid mixture.
Methods : Human liver microsomes (HLM) and recombinant CYP2C8 were used as enzyme sources to determine the rate of 6-hydroxypaclitaxel formation in the absence and presence of 2% BSA.
Result : In the presence of 2% BSA, the mean Km for PAC 6-hydroxylation by HLM was reduced, with a minor effect on mean Vmax. Moreover, BSA reversed the inhibition by fatty acid mixture.
Conclusions : This effect may arises from BSA sequestration of PUFAs that are released from the membrane of in vitro enzyme sources during the course of an incubation.
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| Author |
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| Peer Review Status |
มีผู้ประเมินอิสระ |
| Level of Conference |
ชาติ |
| Type of Proceeding |
Abstract |
| Type of Presentation |
Poster |
| Part of thesis |
false |
| ใช้สำหรับสำเร็จการศึกษา |
ไม่เป็น |
| Presentation awarding |
false |
| Attach file |
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| Citation |
0
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Publication
Journal Publication
ไทย