Persson B, Heykants J, Hedner T
Department of Medicine I and Clinical Pharmacology, Sahlgren's Hospital, Gothenburg, Sweden.
Clin Pharmacokinet. 1991 Apr;20(4):263-79. doi: 10.2165/00003088-199120040-00002.
Ketanserin is a serotonin S2-receptor antagonist introduced for the treatment of arterial hypertension and vasospastic disorders. Plasma concentrations of ketanserin (and some metabolites) can be measured with high performance liquid chromatography using ultraviolet or fluorescence detection, or by radioimmunoassay. The methods are sensitive, accurate and specific. Following oral administration ketanserin is almost completely (more than 98%) and rapidly absorbed and peak concentrations in plasma are reached within 0.5 to 2 hours. It is subject to considerable extraction and metabolism in the liver (first-pass effect) and the absolute bioavailability is around 50%. The compound is extensively distributed to tissues and the volume of distribution is in the order of 3 to 6 L/kg. In plasma ketanserin binds avidly to plasma proteins, mainly albumin, and the free fraction is around 5%. Ketanserin is extensively metabolised and less than 2% is excreted as the parent compound. The major metabolic pathway is by ketone reduction leading to formation of ketanserin-ol which is mainly excreted in the urine. Ketanserin-ol, which by itself does not contribute to the overall pharmacological effect, is partly reoxidised into ketanserin, and it is likely that the terminal half-life of the parent compound is related to the slow ketanserin regeneration from the metabolite. Following intravenous administration plasma ketanserin concentrations decay triexponentially with sequential half-lives of 0.13, 2 and 14.3 h. The terminal half-life is similar after oral administration. Following long term oral dosing (20 or 40 mg twice daily) the pharmacokinetics remain linear and steady-state concentrations, which can be predicted from single-dose kinetics, are reached within 4 days. During long term treatment with the common dosage of 40 mg twice daily, steady-state concentrations fluctuate between 40 micrograms/L (trough) and 100 to 140 micrograms/L (peak). The pharmacokinetic properties of ketanserin are predictable in a wide group of patients and there is no influence from the duration of treatment, age and sex of the patient or concomitant treatment with beta-blockers or diuretics. There is no direct relationship between plasma concentrations of ketanserin and the antihypertensive effect in a group of patients. Side effects, including prolongation of the Q-T interval, are dose-dependent and, at least in the individual patient, related to peak plasma concentrations. In separate studies the pharmacokinetics of ketanserin were investigated in special patient groups, namely the elderly and patients with hepatic and renal insufficiency.(ABSTRACT TRUNCATED AT 400 WORDS)
酮色林是一种5-羟色胺S2受体拮抗剂，用于治疗动脉高血压和血管痉挛性疾病。酮色林（及某些代谢物）的血浆浓度可用高效液相色谱法结合紫外或荧光检测来测定，也可用放射免疫分析法测定。这些方法灵敏、准确且特异。口服后，酮色林几乎完全（超过98%）且迅速被吸收，血浆中在0.5至2小时内达到峰值浓度。它在肝脏中会经历显著的提取和代谢（首过效应），绝对生物利用度约为50%。该化合物广泛分布于组织中，分布容积约为3至6L/kg。在血浆中，酮色林与血浆蛋白，主要是白蛋白，紧密结合，游离部分约为5%。酮色林被广泛代谢，以母体化合物形式排泄的不到2%。主要代谢途径是通过酮还原形成酮色林醇，其主要经尿液排泄。酮色林醇本身对总体药理作用无贡献，部分会再氧化为酮色林，母体化合物的终末半衰期可能与从代谢物缓慢再生酮色林有关。静脉给药后，血浆酮色林浓度呈三指数衰减，相继的半衰期分别为0.13、2和14.3小时。口服给药后的终末半衰期相似。长期口服给药（每日两次，每次20或40mg）时，药代动力学保持线性，4天内达到可根据单剂量动力学预测的稳态浓度。在长期以每日两次40mg的常用剂量治疗期间，稳态浓度在40μg/L（谷值）和100至140μg/L（峰值）之间波动。酮色林的药代动力学特性在广泛的患者群体中是可预测的，不受治疗持续时间、患者年龄和性别或与β受体阻滞剂或利尿剂联合治疗的影响。在一组患者中，酮色林的血浆浓度与降压效果之间无直接关系。副作用，包括Q-T间期延长，呈剂量依赖性，至少在个体患者中与血浆峰值浓度有关。在单独的研究中，对特殊患者群体，即老年人以及肝肾功能不全患者，研究了酮色林的药代动力学。（摘要截选至400字）
