Siegmund W, Zschiesche M, Kallwellis R, Franke G, Schneider T, Sill U, Scherber A, Hüller H
Pharmazie. 1985 Nov;40(11):779-81.
For the quantitative determination of dihydralazine (1) a derivative with acetylacetone in biological material was formed at pH = 4.9, extracted with n-hexane, and measured gaschromatographically with N-P-FID. Acid labile 1 was hydrolyzed with HCl (1 mol/l) for 24 h. The detection limit was 25 nmol/l plasma. Kinetic studies were performed in 16 patients with essential hypertension under steady-state conditions after the oral application of 50 mg 1. The acetylator phenotype was determined with sulfamethazine. Complete dihydralazine plasma level-time courses were found in only 5 cases. The concentrations were below the detection limit in 4 patients for the whole period. Only single values could be registered in the remaining patients. Maximal plasma levels of the free (58-314 nmol/l) and acid labile 1 (147-367 nmol/l) were reached 20-40 min after the application. The elimination half life was 23-47 min for the free 1, 55-92 min for the acid labile 1. Less than 0.5% of the applied drug were excreted into the 24 h urine in its free form, about 0.4% as acid labile derivatives. No correlation could be found between the acetylator phenotype of the patients and the kinetic behaviour of the drug. Preliminary studies concerning the biliary excretion of 1 after i. m. application in two patients with T-drain showed an accumulation of the free compound with bile/plasma ratios up to 7.4.
为了定量测定双肼屈嗪（1），在pH = 4.9的条件下，使其与生物材料中的乙酰丙酮形成衍生物，用正己烷萃取，并用氮磷火焰离子化检测器进行气相色谱测定。酸不稳定的1用1mol/L盐酸水解24小时。检测限为血浆中25nmol/L。对16例原发性高血压患者口服50mg 1后，在稳态条件下进行了动力学研究。用磺胺二甲嘧啶测定乙酰化表型。仅在5例患者中发现了完整的双肼屈嗪血浆浓度-时间过程。4例患者在整个时间段内浓度均低于检测限。其余患者仅能记录到单个值。给药后20 - 40分钟达到游离双肼屈嗪（58 - 314nmol/L）和酸不稳定的1（147 - 367nmol/L）的最大血浆浓度。游离1的消除半衰期为23 - 47分钟，酸不稳定的1为55 - 92分钟。给药药物中以游离形式排泄到24小时尿液中的不到0.5%，约0.4%以酸不稳定衍生物形式排泄。未发现患者的乙酰化表型与药物的动力学行为之间存在相关性。对两名带有T形引流管的患者肌肉注射1后胆汁排泄的初步研究表明，游离化合物在胆汁中蓄积，胆汁/血浆比值高达7.4。
