Pharmacokinetics and pharmacodynamics of propranolol in hypertensive patients after sublingual administration: systemic availability.

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The bioavailability of propranolol depends on the degree of liver metabolism. Orally but not intravenously administered propranolol is heavily metabolized. In the present study we assessed the pharmacokinetics and pharmacodynamics of sublingual propranolol. Fourteen severely hypertensive patients (diastolic blood pressure (DBP) > or = 115 mmHg), aged 40 to 66 years, were randomly chosen to receive a single dose of 40 mg propranolol hydrochloride by sublingual or peroral administration. Systolic (SBP) and diastolic (DBP) blood pressures, heart rate (HR) for pharmacodynamics and blood samples for noncompartmental pharmacokinetics were obtained at baseline and at 10, 20, 30, 60 and 120 min after the single dose. Significant reductions in BP and HR were obtained, but differences in these parameters were not observed when sublingual and peroral administrations were compared as follows: SBP (17 vs 18%, P = NS), DBP (14 vs 8%, P = NS) and HR (22 vs 28%, P = NS), respectively. The pharmacokinetic parameters obtained after sublingual or peroral drug administration were: peak plasma concentration (CMAX): 147 +/- 72 vs 41 +/- 12 ng/ml, P < 0.05; time to reach CMAX (TMAX): 34 +/- 18 vs 52 +/- 11 min, P < 0.05; biological half-life (t1/2b): 0.91 +/- 0.54 vs 2.41 +/- 1.16 h, P < 0.05; area under the curve (AUCT): 245 +/- 134 vs 79 +/- 54 ng h-1 ml-1, P < 0.05; total body clearance (CLT/F): 44 +/- 23 vs 26 +/- 12 ml min-1 kg-1, P = NS. Systemic availability measured by the AUCT ratio indicates that extension of bioavailability was increased 3 times by the sublingual route. Mouth paresthesia was the main adverse effect observed after sublingual administration. Sublingual propranolol administration showed a better pharmacokinetic profile and this route of administration may be an alternative for intravenous or oral administration.