The effect of cadralazine and its active metabolite CGP 22639 on the covalent binding reaction of C4 and C3 has been studied. Trypsin-Sepharose was used to activate radio-labelled C3 and C4 and binding of the radio-labelled protein to the trypsin-Sepharose was measured. Cadralazine inhibited 50% of the binding of C3 and C4 at concentrations of 19 mmol/l and 15 mmol/l, respectively. Its active metabolite was more potent and inhibited 50% of the C3 and C4 binding at concentrations of 8 and 3.5 mmol/l, respectively. These concentrations are much higher than those found in plasma during therapy. This is consistent with the clinical observation that in patients with normal kidney function cadralazine is not an inducer of SLE.

A comparison was made between the results of acetylator phenotyping by isoniazid (INH) half-life measurements based on 5 samples (0-6 h), and by determination of the ratio of monoacetylated (MAD) to unchanged dapsone (DDS) in a single sample obtained 3 h after dapsone intake. In each of 44 subjects examined, there was unequivocal agreement about classification of the subject as a rapid (INH t1/2 less than 2 h; MAD/DDS greater than 0.3) or slow (INH t1/2 greater than 2 h; MAD/DDS less than 0.3) acetylator. It appears that the single-sample (3 h) dapsone test is as reliable as the more laborious and time-consuming INH test for acetylator phenotyping.

The influence of food on the bioavailability of hydralazine in noncoated and coated tablets was examined in 5 healthy males. Each subject received an oral 50-mg dose on four different occasions: two 25-mg noncoated tablets with and without food and one 50-mg coated tablet with and without food. The meal was a standardized breakfast of 440 calories. Venous blood samples were obtained during a 6-hr period, and the plasma concentrations of unmetabolized hydralazine were assessed by a selective and sensitive gas chromatographic method. The results indicate that food enhances the bioavailability of hydralazine 2- to 3-fold both when noncoated and coated tablets are used.

A high-pressure liquid chromatographic technique was developed which allowed concurrent measurement of acetylsalicylic acid (ASA) and salicylic acid (SA) in plasma. ASA was extensively deacetylated to SA not only in vivo but also in vitro, even in frozen plasma. The in vitro conversion could be prevented by physostigmine. In vivo, ASA was eliminated within few hours, whereas SA was continuously present following daily administration of conventional doses of ASA. A slight modification of a similar method, originally developed for naproxen determination [9], was found appropriate for measurement of the SA derivative diflunisal, of two non-SA antiinflammatory agents, indomethacin and indoprofen, and of a related anti-platelet agent, indobufen.

The concentration of "real" and "apparent" (= "real" hydralazine + acid-labile hydrazones) hydralazine in maternal and umbilical plasma obtained at delivery of 6 women treated with hydralazine and atenolol for pregnancy hypertension were measured by gas chromatography. In one of the patients, the concentrations of the same substances were subsequently measured in breast milk. "Apparent" hydralazine reached higher levels in umbilical than in maternal blood. The concentration of "real" hydralazine seemed to be at least as high in the fetus as in the mother. On the other hand, even though the fraction of "real" (i.e. presumably active) hydralazine was greater in milk than in plasma, the total concentration was smaller, and the estimated dose per milk feed of 75 ml would not exceed 0.013 mg. Thus, hydralazine treatment of the pregnant woman would expose her fetus to effective concentrations of the drug, but breast feeding would not result in a clinically relevant concentration in the infant.