Brater D C, Kaojarern S, Benet L Z, Lin E T, Lockwood T, Morris R C, McSherry E J, Melmon K L
Clin Pharmacol Ther. 1980 Nov;28(5):690-4. doi: 10.1038/clpt.1980.222.
A patient with renal acidosis developed unanticipated toxicity after ordinary doses of pseudoephedrine, prompting us to study renal determinants of its elimination. We presumed that our patient accumulated the drug because of her persistently alkaline urine, which would favor tubular resorption of this weak base (pKa = 9.4). We studied normal adults and children and one adult and one child with renal tubular acidosis. Increasing urine pH increased the serum elimination half-life from 1.9 to 21 hr. While urinary pH remained alkaline, renal excretion of pseudoephedrine and its metabolite, norpseudoephedrine, was directly correlated with the flow rate of urine in each subject. Both urine pH and flow are important determinants of the elimination of pseudoephedrine in man and could be critical determinants of unanticipated toxicity.
一名患有肾性酸中毒的患者在服用常规剂量的伪麻黄碱后出现了意外的毒性反应，这促使我们研究其消除的肾脏决定因素。我们推测，我们的患者由于尿液持续呈碱性而积累了该药物，这有利于这种弱碱（pKa = 9.4）的肾小管重吸收。我们研究了正常成人和儿童以及一名患有肾小管酸中毒的成人和一名儿童。尿液pH值升高使血清消除半衰期从1.9小时增加到21小时。当尿液pH值保持碱性时，伪麻黄碱及其代谢产物去甲伪麻黄碱的肾排泄与每个受试者的尿流率直接相关。尿液pH值和流速都是人体中伪麻黄碱消除的重要决定因素，并且可能是意外毒性的关键决定因素。
