Interaction between oral hydralazine and propranolol. II. Assessment of altered splanchnic blood flow as the determinant of altered presystemic extraction

H Corbett, CM Cahill, B Heinzow, PM Harrison, AJ Byrne and AJ McLean

Coadministration of p.o. hydralazine and d-propranolol or dl- propranolol in six conscious dogs caused a significant increase in peak plasma concentration and area under the p.o. plasma concentration-time curve of propranolol (P less than .01, P less than .01, peak plasma concentration; P less than .01 and P less than .05, area under the plasma concentration-time curve; d-propranolol and dl-propranolol, respectively). Coadministration of p.o. hydralazine with p.o. dl- propranolol resulted in a small trend toward an increase in systemic clearance of i.v. dl-[3H]propranolol; however, this did not reach statistical significance (P less than .2, P less than .1, d-propranolol and dl-propranolol, respectively). When a mixture of d-propranolol and 14C-labeled dl-propranolol was administered into the jejunum of seven anesthetised dogs, the absorption into portal vein of the 14C-labeled dl-propranolol paralleled closely that of d-propranolol both in terms of time to peak and absorption as measured by a percentage of total area under the plasma concentration-time curve at an arbitrary time (10 min) postdose. Assessment of hepatic extraction (E) showed similar close parallels (d-propranolol, E = 0.85 +/- 0.02; dl-[14C]propranolol, E = 0.86 +/- 0.03: mean +/- S.E.M., n = 5, P less than .70). Hepatic extraction of propranolol and blood flow in mesenteric artery and hepatic artery were measured in 23 anesthetised dogs given a constant infusion of d-propranolol into portal vein (11 micrograms/kg/min), made up to 6 control and 17 hydralazine-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 239, Issue 2, pp. 517-521, 11/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics