Fischer D, Breyer-Pfaff U
Department of Toxicology, University of Tübingen, Germany.
Eur J Drug Metab Pharmacokinet. 1997 Apr-Jun;22(2):151-4. doi: 10.1007/BF03189799.
The H1-antagonist diphenhydramine can undergo direct glucuronidation at its tertiary amino group with formation of a quaternary ammonium glucuronide. The intraindividual variability in the amount of N-glucuronide excretion in urine was investigated in two female volunteers who repeatedly took single doses of 25 mg diphenhydramine hydrochloride without and with concomitant administration of ascorbic acid or ammonium chloride for urine acidification. Another two female and four male subjects underwent single tests without and with additional ascorbic acid. Diphenhydramine N-glucuronide quantities in urine differed significantly among subjects and ranged between 2.7% and 14.8% of the dose within 8 h. Neither ascorbic acid nor ammonium chloride significantly influenced the quantity of N-glucuronide in urine, but ammonium chloride, that in contrast to ascorbic acid proved effective in lowering urinary pH, increased the excretion of the parent drug.
H1拮抗剂苯海拉明可在其叔氨基处直接发生葡萄糖醛酸化，形成季铵葡萄糖醛酸苷。在两名女性志愿者中研究了尿中N - 葡萄糖醛酸排泄量的个体内变异性，她们在未服用和同时服用抗坏血酸或氯化铵以使尿液酸化的情况下，多次单次服用25mg盐酸苯海拉明。另外两名女性和四名男性受试者在未服用和额外服用抗坏血酸的情况下进行了单次试验。尿中苯海拉明N - 葡萄糖醛酸苷的量在受试者之间有显著差异，在8小时内占剂量的2.7%至14.8%之间。抗坏血酸和氯化铵均未显著影响尿中N - 葡萄糖醛酸苷的量，但氯化铵与抗坏血酸不同，被证明可有效降低尿液pH值，增加母体药物的排泄。
