Fredericson Overø K, Toft B, Christophersen L, Gylding-Sabroe J P
Psychopharmacology (Berl). 1985;86(3):253-7. doi: 10.1007/BF00432209.
The kinetics of the antidepressant drug citalopram, a specific 5-HT uptake inhibitor, has been investigated in 11 elderly patients (age 73-90) and compared to previous data from younger patients and volunteers. The recorded steady state citalopram levels of 140-545 nM after a once-daily 20-mg dose were up to four times higher than expected from data in younger patients and volunteers. The biological half-life (1.5-3.75 days) and estimated systemic clearance (0.08-0.3 1/min) also differed from data in younger individuals (1.5 days and 0.4 1/min, respectively). Clearance values generally decreased with increasing age. Drug/metabolite ratios were higher in patients with the longest half-lives and lowest citalopram clearance, indicating reduced metabolic activity. No reduction in renal clearance was indicated by urine data, obtained for two of the patients. The study suggests that daily doses of 5-20 mg give approximately the same steady state plasma levels in elderly patients as doses of 40 mg in younger, and that this is due to reduced rates of metabolism in the elderly.
抗抑郁药物西酞普兰是一种特异性5-羟色胺摄取抑制剂,对11名老年患者(年龄73 - 90岁)的药代动力学进行了研究,并与之前年轻患者和志愿者的数据进行了比较。每日一次服用20毫克剂量后,记录的西酞普兰稳态血药浓度为140 - 545纳摩尔,比年轻患者和志愿者的数据高出四倍。生物半衰期(1.5 - 3.75天)和估计的全身清除率(0.08 - 0.3升/分钟)也与年轻个体的数据不同(分别为1.5天和0.4升/分钟)。清除率值通常随年龄增长而降低。半衰期最长且西酞普兰清除率最低的患者,其药物/代谢物比值更高,表明代谢活性降低。对两名患者获取的尿液数据未显示肾清除率降低。该研究表明,每日5 - 20毫克剂量在老年患者中产生的稳态血浆水平与年轻患者中40毫克剂量产生的水平大致相同,这是由于老年人代谢速率降低所致。