Influence of hydralazine on the pharmacokinetics of orally administered d-propranolol and lidocaine in conscious dogs.
A study was conducted on the influence of oral coadministration of hydralazine (H) on the pharmacokinetics of d-propranolol (P) and lidocaine (L) in 6 conscious dogs. They were given an oral solution containing P (2 mg/kg) and L (15 mg/kg) alone or together with 25 mg H. Plasma concentrations of P and L and the metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX) were measured by specific HPLC methods. Concomitant administration of H caused a significant (p less than 0.05) increase in P peak concentrations (Cmax, 34 +/- 5: 73 +/- 10 ng/ml) and the area under plasma concentration time curve (AUC, 142 +/- 18: 254 +/- 56 ng/ml X hr) of P with significant (p less than 0.05) 24% reduction of the apparent oral clearance. The time to reach peak concentrations (Tmax) and the terminal half life (t1/2 beta) were not altered. In contrast to the pattern seen with P the disposition of L was not affected by H. The change in presystemic clearance of P by H cannot be explained by a general underlying mechanism such as an alteration in liver blood flow alone or portal-systemic shunting, since then the pharmacokinetics of L should parallel those of P. It is speculated that other mechanisms, most likely alteration of P metabolism, are primarily responsible for the observed interaction between P and H.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004338:Drug Combinations; D004347:Drug Interactions; D006207:Half-Life; D006830:Hydralazine / Q000494:pharmacology*; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood*; D011433:Propranolol / Q000008:administration & dosage / Q000097:blood*
D004338:Drug Combinations; D006830:Hydralazine; D008012:Lidocaine; D011433:Propranolol; C001306:glycinexylidide; C001173:monoethylglycinexylidide