The pharmacokinetic and pharmacodynamic interaction between lacidipine and propranolol in healthy volunteers.
The pharmacokinetic and pharmacodynamic profiles of lacidipine, a 1,4-dihydropyridine calcium antagonist, and the beta-adrenoceptor blocker propranolol were determined alone and in combination in 24 healthy male volunteers. One group (I) of 12 subjects received a single oral dose of 4 mg lacidipine on two separate occasions, which was taken together with a single oral dose of either 160 mg propranolol or placebo; a second group (II) of 12 subjects received propranolol on two occasions, taken with either lacidipine or placebo. Propranolol significantly decreased the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of lacidipine (by 38% and 42%, respectively) whereas lacidipine significantly increased the Cmax and AUC of propranolol (by 35% and 26%, respectively); neither the time to maximum plasma concentration (tmax) nor the terminal half-life (t 1/2) were affected. With regard to the pharmacodynamics, in Group I, there was a greater reduction in supine systolic blood pressure (6 mm Hg) and diastolic blood pressure (4 mm Hg) compared to the reduction produced by lacidipine alone, and pulse rate was approximately 5 beats/min less. In Group II, a significantly greater reduction (6 mm Hg) in supine systolic blood pressure compared to the reduction produced by propranolol alone occurred, but there was no marked difference in supine diastolic blood pressure and pulse rate. In conclusion, a modest pharmacokinetic and pharmacodynamic interaction is evident and should be evaluated further in patients with hypertension.
Hall
S T
ST
Department of Clinical Pharmacology, Glaxo Group Research Ltd., Middlesex, England.
Harding
S M
SM
Hassani
H
H
Keene
O N
ON
Pellegatti
M
M
D000284:Administration, Oral; D000328:Adult; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D004095:Dihydropyridines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D006801:Humans; D008297:Male; D011433:Propranolol / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060285:lacidipine; D011433:Propranolol