| Autor: |
Tagen M; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA., Zhuang Y, Zhang F, Harstead KE, Shen J, Schaiquevich P, Fraga CH, Panetta JC, Waters CM, Stewart CF |
| Jazyk: |
angličtina |
| Zdroj: |
Drug metabolism letters [Drug Metab Lett] 2010 Dec; Vol. 4 (4), pp. 195-201. |
| DOI: |
10.2174/187231210792928251 |
| Abstrakt: |
The ATP-binding cassette transporters P-glycoprotein (ABCB1, MDR1) and multidrug resistance protein 4 (MRP4) efflux irinotecan and its active metabolite SN-38 in vitro, and thus may contribute to system clearance of these compounds. Mdr1a/b(-/-), Mrp4(-/-), and wild-type mice were administered 20 or 40 mg/kg irinotecan, and plasma samples were collected for 6 hours. Irinotecan and SN-38 lactone and carboxylate were quantitated and data were analyzed with nonlinear mixed-effects modeling. Mdr1a/b genotype was a significant covariate for the clearance of both irinotecan lactone and SN-38 lactone. Exposures to irinotecan lactone and SN-38 lactone after a 40 mg/kg dose were 1.6-fold higher in Mdr1a/b(-/-) mice compared to wild-type mice. Plasma concentrations of irinotecan lactone, irinotecan carboxylate, and SN-38 lactone in Mrp4(-/-) mice were similar to the wild-type controls. These results suggest that P-gp plays a role in irinotecan and SN-38 elimination, but Mrp4 does not affect irinotecan or SN-38 plasma pharmacokinetics. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
