1 Ranitidine single dose pharmacokinetics and absolute bioavailability have been studied in five healthy male volunteers. Following an overnight fast, 150 mg was given intravenously as a bolus injection or orally as a tablet formulation to each subject on separate occasions. 2 Following intravenous administration, plasma levels declined biexponentially. The mean (+ s.d.) distribution half-life (t2¼a) was 6.6 + 1.6 min; plasma half-life (t,12/3) was 1.7 + 0.2 h; the volume of distribution (V) was 96 + 9 1; total body clearance (CL) was 647 + 94 ml/min and renal clearance (CLR) 520 + 123 ml/min. 3 Following oral administration plasma levels showed a bimodal pattern with a first peak at 1.1 + 0.4 h and a second peak at 3 + 0 h. The absolute availability was 60 + 17%. The plasma half-life (t/2) of 2.3 + 0.4 h was significantly longer (P < 0.05) after oral than after i.v. administration. 4 Renal excretion of unchanged ranitidine accounted for 79 + 9% of the dose after i.v. administration and for 27 + 7% after oral administration. 5 Our results suggest a more extensive biotransformation of ranitidine and biliary excretion of metabolites after oral administration while i.v. administered ranitidine is preferentially excreted unchanged in the urine.

Single doses of enalapril maleate 10 mg and frusemide 80 mg do not significantly affect the pharmacokinetics of each other when taken concomitantly. Their concomitant use may be associated with more adverse effects than with the individual entities.