Zorbas M, Owens S M, Plunkett L M, Bui H
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205.
Drug Metab Dispos. 1989 Nov-Dec;17(6):641-5.
Using adult male Sprague-Dawley rats, we examined the blood protein binding and pharmacokinetics of the potent phencyclidine (PCP) receptor ligand 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP). The average percentage of unbound [3H]TCP in rat serum was 42 +/- 6% and the [3H]TCP blood to plasma ratio was 0.98 +/- 0.03 (mean +/- SD, n = 5 in both studies). For the pharmacokinetic studies, [3H]TCP and 1 mg/kg unlabeled TCP were administered as an iv bolus dose. The average [3H]TCP elimination half-life was 2.1 hr. In contrast, total radioactivity in the plasma had a much longer half-life, suggesting much slower metabolite elimination. The average distribution volumes were 27 +/- 17, 15.6 +/- 6.2, and 5.6 +/- 3.0 liters/kg for V beta, Vss, and Vc, respectively. Total body and renal clearance values were 132 +/- 45 and 1.1 +/- 0.4 ml/min/kg, respectively. When TCP pharmacokinetic parameters were compared to PCP pharmacokinetic data in rats from a previous study, a strikingly similar pharmacokinetic profile was found. These data indicated that TCP and PCP are equivalent, from a pharmacokinetic point of view, and that the higher pharmacological potency of TCP over PCP is probably due to receptor-mediated differences.
我们使用成年雄性斯普拉格-道利大鼠，研究了强效苯环己哌啶（PCP）受体配体1-[1-(2-噻吩基)环己基]哌啶（TCP）的血液蛋白结合情况和药代动力学。大鼠血清中未结合的[3H]TCP的平均百分比为42±6%，[3H]TCP的血药比与血浆比为0.98±0.03（均值±标准差，两项研究中n均为5）。在药代动力学研究中，[3H]TCP和1mg/kg未标记的TCP以静脉推注剂量给药。[3H]TCP的平均消除半衰期为2.1小时。相比之下，血浆中的总放射性半衰期要长得多，这表明代谢物的消除要慢得多。Vβ、Vss和Vc的平均分布容积分别为27±17、15.6±6.2和5.6±3.0升/千克。全身清除率和肾脏清除率分别为132±45和1.1±0.4毫升/分钟/千克。当将TCP的药代动力学参数与先前一项研究中大鼠的PCP药代动力学数据进行比较时，发现了惊人相似的药代动力学特征。这些数据表明，从药代动力学角度来看，TCP和PCP是等效的，TCP比PCP更高的药理活性可能是由于受体介导的差异。
