PHARMACOKINETICS AND PHARMACODYNAMICS OF PROPRANOLOL IN HYPERTENSIVE PATIENTS AFTER SUBLINGUAL ADMINISTRATION - SYSTEMIC AVAILABILITY

The bioavailability of propranolol depends on the degree of liver meta bolism. Orally but not intravenously administered propranolol is heavi ly metabolized. In the present study we assessed the pharmacokinetics and pharmacodynamics of sublingual propranolol. Fourteen severely hype rtensive patients (diastolic blood pressure (DBP) greater than or equa l to 115 mmHg), aged 40 to 66 years, were randomly chosen to receive a single dose of 40 mg propranolol hydrochloride by sublingual or peror al administration. Systolic (SBP) and diastolic (DBP) blood pressures, heart rate (HR) for pharmacodynamics and blood samples for noncompart mental pharmacokinetics were obtained at baseline and at 10, 20, 30, 6 0 and 120 min after the single dose. Significant reductions in BP and HR were obtained, but differences in these parameters were not observe d when sublingual and peroral administrations were compared as follows : SEP (17 vs 18%, P = NS), DBP (14 vs 8%, P = NS) and HR (22 vs 28%, P = NS), respectively. The pharmacokinetic parameters obtained after su blingual or peroral drug administration were: peak plasma concentratio n (C-MAX): 147 +/- 72 vs 41 +/- 12 ng/ml, P<0.05; time to reach C-MAX (T-MAX): 34 +/- 18 vs 52 +/- 11 min, P<0.05; biological half-life (t1/ 2(b)): 0.91 +/- 0.54 vs 2.41 +/- 1.16 h, P<0.05; area under the curve (AUC(T)): 245 +/- 134 vs 79 +/- 54 ng h(-1) ml(-1), P<0.05; total body clearance (CLT/F): 44 +/- 23 vs 26 +/- 12 mi min(-1) kg(-1), P = NS. Systemic availability measured by the AUC(T) ratio indicates that exte nsion of bioavailability was increased 3 times by the sublingual route . Mouth paresthesia was the main adverse effect observed after subling ual administration. Sublingual propranolol administration showed a bet ter pharmacokinetic profile and this route of administration may be an alternative for intravenous or oral administration.