Calcium channel antagonists and cyclosporine metabolism: in vitro studies with human liver microsomes.
The effects of four Ca2+ channel antagonists on the metabolism of cyclosporine (CsA) by human liver microsomes (n = 4) in vitro have been examined. Nicardipine produced marked inhibition of both M17 and M21 (IC50 = 7.0 microM) formation. In contrast nifedipine produced less than 20% inhibition of M17 and M21 even at the highest concentration examined (50 microM). Diltiazem data were comparable to those for nifedipine. Verapamil (50 microM) produced 30 and 28% inhibition of M17 and M21 formation, respectively. These findings give a basis to the increase in CsA blood concentrations seen in transplant patients who are also given nicardipine.
Tjia
J F
JF
Department of Pharmacology and Therapeutics, University of Liverpool.
Back
D J
DJ
Breckenridge
A M
AM
D000328:Adult; D002121:Calcium Channel Blockers / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003524:Cyclosporins / Q000378:metabolism*; D004110:Diltiazem / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008875:Middle Aged; D009529:Nicardipine / Q000378:metabolism; D011863:Radioimmunoassay; D014700:Verapamil / Q000378:metabolism
D002121:Calcium Channel Blockers; D003524:Cyclosporins; D014700:Verapamil; D009529:Nicardipine; D004110:Diltiazem