Determination of ISF-2405, an active metabolite of cadralazine, in plasma and tissues by radioimmunoassay.

A radioimmunoassay has been developed which makes possible sensitive and specific determination of an active metabolite of cadralazine, (+/-)-6-[ethyl(2-hydroxypropyl)amino]-3-hydrazinopyridazine (ISF-2405), in plasma and tissues. On account of its lability in a sample solution, ISF-2405 in biological samples was selectively derivatized to a stable form, (+/-)-6-[ethyl(2-hydroxypropyl)amino]-3-(3,5-dimethyl-1-pyrazolyl) pyridazine (ISF-3349), by treatment with acetylacetone. The concentration of ISF-2405 was determined by the assay of the resultant ISF-3349. Antiserum against ISF-3349 was elicited in guinea pigs immunized with the ISF-3349 derivative coupled with bovine serum albumin. The obtained antiserum was highly specific for ISF-3349, and did not cross-react with either cadralazine or its metabolites. [Pyrazole-4-3H]labeled ISF-3349 with a specific activity of 13.9 Ci/mmol was used as the radioligand. Assays of ISF-2405 in plasma and tissues were possible over the concentration range from 0.4 to 6.4 ng/ml with 1 ml of plasma, and from 2 to 64 ng/g with 100 mg of tissue. Plasma and blood vessel levels of ISF-2405 in rats after single oral administration of cadralazine have also been determined by the present method.

Comparative study of endralazine and hydralazine for the treatment of hypertension uncontrolled by a beta-blocker and diuretic.

Endralazine and hydralazine were compared in a randomized double-blind, parallel group study lasting 1 year in 30 patients with essential hypertension inadequately controlled by a beta-blocker and a diuretic. Dosage ranged from 10 mg to 30 mg endralazine per day and from 75 mg to 200 mg hydralazine per day according to patient response. The results showed that endralazine was at least as effective as hydralazine in reducing blood pressure. Patients' tolerance, assessed by drop-out rate, was significantly better (p less than 0.05) in the endralazine group. No cases were found of drug-induced lupus-like syndrome on endralazine as opposed to 2 cases with hydralazine. The dose of endralazine required much less adjustment than that of hydralazine.