Summary
Six healthy volunteers received single 20-mg intravenous (IV) and 80-mg oral doses of propranolol on two occasions in random sequence. Serum propranolol concentrations were determined by gas chromatography in multiple samples drawn during 24 h after each dose. Mean (±SE) kinetic variables for IV propranolol were: elimination half-life (t1/2β), 5.3 (±0.6) h; volume of distribution, 2.3 (±0.3) l/kg; total clearance, 4.9 (±0.3) ml/min/kg; predicted extraction ratio, 0.23 (±0.02). After single oral doses, t1/2β (3.8±0.2 h) tended to be smaller than after the IV dose, and actual systemic availability (0.60±0.07) was less than that based on the predicted extraction ratio. During multiple oral dosage (80 mg every 12 h), observed steady state serum levels (47±5 ng/ml) tended to be less than those predicted based on the single oral dose (61±5 ng/ml), thus providing no evidence for reduced propranolol clearance at steady-state. Echocardiographic measurements of left ventricular performance (posterior wall velocity, diastolic dimensions) made during the single-dose oral study indicated significant impairment of function; impairment was maximal at 3 h post-dosage, and corresponded to the time of the peak serum propranolol concentration (341 ng/ml).
Zusammenfassung
Sechs gesunde Probanden erhielten in randomisierter Reihenfolge 20 mg Propranolol i.v. und 80 mg oral. Die Serumkonzentrationen an Propranolol wurden gaschromatographische über 24 h nach jeder Dosis bestimmt. Die kinetischen Variablen für Propranolol (±SE) lauten: Eliminationshalbwertzeit (t1/2β):5,3 h±0,6 h; Verteilungsvolumen: 2,3±0,3 l/kg; totale Clearance 4,9±0,3 ml/min/kg; berechnete Extraktionsrate: 0,23±0,02. Nach oraler Propranololgabe war t1/2β mit 3,8±0,2 h kürzer als nach i.v. Applikation und die systemische Verfügbarkeit mit 0,60±0,07 geringfügig niedriger als von der Extraktionsrate zu erwarten. Die steady state Serumkonzentrationen unter Mehrfachgabe (80 mg alle 12 h) lagen mit 47±5 ng/ml niedriger als die nach den Ergebnissen der Einmaldosis berechneten Spiegel (61±5 ng/ml). Die echokardiographisch bestimmten linksventrikulären Funktionsparameter (Kontraktionsgeschwindigkeit der Hinterwand, enddiastolischer Durchmesser), die unter der einmaligen 80 mg Dosis bestimmt wurden, zeigten eine Beeinträchtigung der Ventrikelfunktion mit einem Maximum 3 h nach Propranolol-Applikation. Dieser Zeitpunkt korrelierte mit den maximalen Serumkonzentrationen (341 ng/ml).
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Supported in part by Grant Oc 10/6-3 from Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, FRG; and by Grant MH-34223 from the United States Public Health Service
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Ochs, H.R., Grube, E., Greenblatt, D.J. et al. Kinetics and cardiac effects of propranolol in humans. Klin Wochenschr 60, 521–525 (1982). https://doi.org/10.1007/BF01756098
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DOI: https://doi.org/10.1007/BF01756098