Intravenous diltiazem and CYP3A-mediated metabolism.
OBJECTIVE
To study whether intravenous diltiazem, a calcium channel blocker commonly prescribed for hypertension and stable angina, is an inhibitor of the CYP3A enzymes by using oral lovastatin, an HMG Co-A reductase inhibitor, as a substrate.


METHODS
Ten healthy volunteers were studied in a randomized two-way crossover design. The two arms were 1) administration of a 20 mg dosage of lovastatin orally and 2) administration of a 20 mg dosage of lovastatin orally 1 h after an intravenous loading dosage and constant infusion of diltiazem. Blood samples were collected up to 25 h in order to quantify lovastatin and diltiazem concentrations in the separated serum. Lovastatin and diltiazem concentrations were quantified by GC-MS and h.p.l.c., respectively.


RESULTS
Intravenous diltiazem did not significantly affect the oral AUC, Cmax, t(1/2), or tmax of lovastatin.


CONCLUSIONS
These data suggest that the interaction of lovastatin with diltiazem does not occur systemically and is primarily a first-pass effect. Thus, drug interactions with diltiazem may become evident when a patient is moved from intravenous to oral dosing.
Masica
A L
AL
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Wishard Memorial Hospital, OPW 320, 1001 West 10th Street, Indianapolis, IN 46202, USA.
Azie
N E
NE
Brater
D C
DC
Hall
S D
SD
Jones
D R
DR
D000328:Adult; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004110:Diltiazem / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008148:Lovastatin / Q000493:pharmacokinetics; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*
D000924:Anticholesteremic Agents; D002317:Cardiovascular Agents; D003577:Cytochrome P-450 Enzyme System; D008148:Lovastatin; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D004110:Diltiazem