Duration of hydralazine action in hypertension

Abstract

The effect on blood pressure of giving hydralazine orally, 300 mg per day divided into 2, 3, and 4 doses, was studied in 4 hypertensive patients. In the treatment of chronic hypertension, hydralazine is conventionally given in 4 divided doses per day, and this schedule of prescribing

Plasma concentration and acetylator phenotype determine response to oral hydralazine.

“…11 -" Since HPH produces no hypotensive effect in the rabbit," rat (Clementi, unpublished data), and dog, 18 it presumably does not contribute to the hypotensive effect of administered hydralazine in the human. Inclusion of a large and variable proportion of HPH in the nonspecific assay results is ample basis for the absence of a good correlation of plasma concentration with antihypertensive effect.…”

“…11 The most abundant component of apparent hydralazine is the hydralazine pyruvic acid hydrazone (HPH), 18 ' u which does not reduce BP in animals. "• " In addition, there is need for a more quantitative estimate than is now available of the extent to which interindividual differences in plasma hydralazine concentration may account for differences in BP response.…”

COMPARATIVE EVALUATION OF THE in vitro EFFECTS OF HYDRALAZINE AND HYDRALAZINE ACETONIDE ON ARTERIAL SMOOTH MUSCLE

“…This possibility is of significance because of previous evidence that hydralazine and/or metabolites preferentially concentrate by 'tight' binding within blood vessel walls (Perry, Comens & Yunice, 1962;Moore-Jones & Perry, 1966;Wagner, 1973;Keberle, Faigle, Hedwall, Riess & Wagner, 1973), in an active form (Moore-Jones & Carmody, 1966). It has been thought likely that this tissue binding provides the basis for pharmacokinetic 'deep compartments' (Lesser, Israili, Davis & Dayton, 1974;O'Malley et al 1975). These 'sequestered' compounds were considered to provide one possible mechanism of mediation of the prolonged effects of hydralazine (Keberle et al, 1973;O'Malley et al, 1975).…”

“…It has been thought likely that this tissue binding provides the basis for pharmacokinetic 'deep compartments' (Lesser, Israili, Davis & Dayton, 1974;O'Malley et al 1975). These 'sequestered' compounds were considered to provide one possible mechanism of mediation of the prolonged effects of hydralazine (Keberle et al, 1973;O'Malley et al, 1975). The results described here would tend to discount the functional significance of 'irreversibly' bound 14C-labelled compounds found in blood vessel walls following the administration of ["4C]-hydralazine to intact animals.…”

“…Pharmacodynamic studies in humans have shown that the duration of the hypotensive effects of hydralazine is greater than expected relative to its concentration in blood (O'Malley, Segal, Israili, Boles, McNay & Dayton, 1975). It The development of techniques utilizing combined gas-liquid chromatography and mass spectrometry (g.l.c.-m.s.)…”