Clinical pharmacokinetics of amlodipine.
Amlodipine is a dihydropyridine calcium antagonist drug with distinctive pharmacokinetic characteristics which appear to be attributable to a high degree of ionisation. Following oral administration, bioavailability is 60 to 65% and plasma concentrations rise gradually to peak 6 to 8h after administration. Amlodipine is extensively metabolised in the liver (but there is no significant presystemic or first-pass metabolism) and is slowly cleared with a terminal elimination half-life of 40 to 50h. Volume of distribution is large (21 L/kg) and there is a high degree of protein binding (98%). There is some evidence that age, severe hepatic impairment and severe renal impairment influence the pharmacokinetic profile leading to higher plasma concentrations and longer half-lives. There is no evidence of pharmacokinetic drug interactions. Amlodipine shows linear dose-related pharmacokinetic characteristics and, at steady-state, there are relatively small fluctuations in plasma concentrations across a dosage interval. Thus, although structurally related to other dihydropyridine derivatives, amlodipine displays significantly different pharmacokinetic characteristics and is suitable for administration in a single daily dose.
Meredith
P A
PA
University Department of Medicine and Therapeutics, Stobhill General Hospital, Glasgow.
Elliott
H L
HL
D000042:Absorption; D017311:Amlodipine; D000787:Angina Pectoris / Q000188:drug therapy; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008099:Liver / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution
D002121:Calcium Channel Blockers; D017311:Amlodipine; D009543:Nifedipine