Eight normal male volunteers received 80mg doses of propranolol by the oral and rectal routes and 2.2 mg by intravenous administration in a crossover fashion. Plasma concentrations of propranolol were measured by a gas chromatographic method using an electron capture detector. Individual subject concentration-time data were analysed and results indicated that the data fit a two compartment model with first order absorption. An approximately two-fold higher plasma propranolol concentration was observed after rectal administration as compared with oral dosing. Statistical analysis of the difference in the total AUCs indicates a significantly higher bioavailability of propranolol administered by the rectal route. The reduced bioavailability after oral administration indicates a substantial first pass effect but that it is possible to bypass the liver, at least partially, by giving the drug rectally to man.
KEY WORDS Propranolol First pass effect Pharmacokinetics Rectal absorption Bioavailability
I N T R O D U C T I O N
T h e route of drug administration can markedly affect the extent and time course of drug action as well as the pattern of drug distribution within the patient. Highly cleared drugs show substantially decreased bioavailability following oral administration due t o metabolic breakdown in the liver o r gut wall. This phenomenon is known as the first pass effect and has been demonstrated for many drugs such as aspirin,' p r ~p r a n o l o l , ~~~ l i d ~c a i n e , ~ p r ~p o x y p h e n e , ~ and nitroglycerin.' Furthermore, the first pass elimination markedly contributes to the inter-individual variability in drug plasma