Effects of diltiazem on the pharmacokinetics of nifedipine.
To evaluate the effect of diltiazem pretreatment (60 mg three times a day for 3 days) on pharmacokinetics and pharmacodynamic effect of nifedipine, six healthy subjects received 20 mg nifedipine orally on two occasions using a double-blind cross-over, placebo-controlled method. Diltiazem induced a marked increment of the area under the plasma concentration-time curve (AUC) for nifedipine by a mean of 140% and reduced the total body clearance (Cl) from 0.0043 +/- 0.0019 to 0.0017 +/- 0.0006 ml/min/kg (p less than 0.05, mean +/- SD). The biological half-life (t1/2) of nifedipine was prolonged from 2.46 +/- 0.65 to 3.21 +/- 0.92 h (p less than 0.05) without any changes in indocyanine green (ICG) clearance. Diltiazem did not produce significant changes of AUC, Cl, and t1/2 for the acid metabolite of nifedipine. Blood pressure (BP) after nifedipine administration with diltiazem pretreatment was more decreased than that without diltiazem. Both a decreased hepatic clearance and an increased bio-availability of nifedipine by diltiazem probably explain the significant changes in pharmacokinetics and hemodynamics of nifedipine. A clinically important drug interaction may occur with nifedipine when diltiazem is administered concurrently.
Ohashi
K
K
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Tateishi
T
T
Sudo
T
T
Sakamoto
K
K
Toyosaki
N
N
Hosoda
S
S
Toyo-oka
T
T
Sugimoto
K
K
Kumagai
Y
Y
Ebihara
A
A
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D004347:Drug Interactions; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007208:Indocyanine Green; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000493:pharmacokinetics* / Q000494:pharmacology
D004110:Diltiazem; D009543:Nifedipine; D007208:Indocyanine Green