Spigset O, Hägg S, Stegmayr B, Dahlqvist R
Division of Clinical Pharmacology, Norrland University Hospital, Umeå, Sweden.
Eur J Clin Pharmacol. 2000 Dec;56(9-10):699-703. doi: 10.1007/s002280000205.
To study the effects of severe renal failure and haemodialysis on the pharmacokinetics of citalopram.
Four patients with renal failure undergoing haemodialysis and eight healthy controls were given a single dose of citalopram. The concentrations of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were measured in serum and urine. On a different day, the four patients undergoing haemodialysis were given another single dose of citalopram, and the drug concentrations were measured in serum from the artery leading to the dialyser and in the dialysate. In addition, one anuric patient treated with citalopram on a regular basis was included in the study.
There were no significant differences between the two groups in any of the pharmacokinetic parameters with the exception of the renal clearance of citalopram, which was significantly lower in the renal failure group than in the control group (1.70 ml/min versus 66.2 ml/min, P<0.001). Oral clearance of citalopram was almost identical in the two groups (452 ml/min versus 456 ml/min). The process of haemodialysis cleared about 1% of the dose as citalopram and 1% as desmethylcitalopram only.
Severe renal failure does not affect the pharmacokinetics of citalopram and modification of the usual citalopram dose does thus not seem to be necessary. The contribution of haemodialysis to the total elimination of citalopram is negligible.
研究严重肾衰竭及血液透析对西酞普兰药代动力学的影响。
对4例接受血液透析的肾衰竭患者和8名健康对照者给予单剂量西酞普兰。测定血清和尿液中西酞普兰及其代谢产物去甲基西酞普兰和双去甲基西酞普兰的浓度。在另一天,对4例接受血液透析的患者再次给予单剂量西酞普兰,并测定通向透析器的动脉血清和透析液中的药物浓度。此外,研究纳入1例长期接受西酞普兰治疗的无尿患者。
除西酞普兰的肾清除率外,两组的任何药代动力学参数均无显著差异,肾衰竭组的西酞普兰肾清除率显著低于对照组(1.70 ml/min对66.2 ml/min,P<0.001)。两组西酞普兰的口服清除率几乎相同(452 ml/min对456 ml/min)。血液透析过程仅清除约1%剂量的西酞普兰和去甲基西酞普兰。
严重肾衰竭不影响西酞普兰的药代动力学,因此似乎无需调整西酞普兰的常用剂量。血液透析对西酞普兰总清除的贡献可忽略不计。