03/10/2007 - Role of transporters in drug ADME
Schmitt U, Abou El-Ela A, Guo LJ, Glavinas H, Krajcsi P, Baron JM, Tillmann C, Hiemke C, Langguth P, Härtter S
J Neural Transm. 2006 Jul;113(7):787-801. Epub 2005 Oct 27.
The importance of P-glycoprotein (P-gp) in the pharmacokinetics of amisulpride and the effects of a P-gp inhibitor cyclosporine A (CsA) was investigated both, in vitro and in vivo. In vitro and in vivo results indicated amisulpride as a substrate of P-gp. Amisulpride was not metabolized by rat liver microsomes. Open field behavior showed time dependent abolishment in locomotion by amisulpride (50 mg kg(-1)). Co-administration of CsA (50 mg kg(-1)) resulted in a higher and significantly longer antipsychotic effect (24 h after drug administration). Accordingly, the area under concentration-time curve in serum and brain was higher in CsA co-treated rats (13.5 vs. 29.8 micromol h l(-1) for serum and 2.16 vs 2.98 micromol h l(-1) for brain tissue) while renal clearance was not affected. These results pointed to a pharmacokinetic drug interaction between CsA and amisulpride most likely caused by inhibition of P-gp.open_in_new Read the Source