Glotzbach R K, Preskorn S H
Psychopharmacology (Berl). 1982;78(1):25-7. doi: 10.1007/BF00470582.
A previously reported method of measuring tricyclic antidepressant concentrations in brain tissue and plasma was used to measure amitriptyline (AMI) in rats following drug administration using different routes, doses, and time intervals. In rats given AMI intraperitoneally (IP), brain concentrations increased during the first 30 min after drug administration and then declined. Brain concentrations increased linearly with changes in IP dosage and increased logarithmically with changes in intravenous dosage. No simple relationship existed between brain and plasma concentrations in acutely dosed rats. However, a linear relationship existed between plasma and brain concentrations in chronically treated animals (r = 0.96, P less than 0.001). The brain:plasma drug ratios observed in chronically treated rats corresponded to ratios reported in man. Thus, conclusions drawn from these studies can probably be extrapolated to the clinical situation. Based on our data, the molar concentration of drug achieved on therapeutic doses is 10(-5)--10(-6) M. This information may aid in understanding the clinical relevance of in vitro drug: receptor binding studies which are typically reported in molar concentrations.
采用先前报道的测量脑组织和血浆中三环类抗抑郁药浓度的方法，在大鼠经不同给药途径、剂量和时间间隔给予药物后，测量阿米替林（AMI）的浓度。给大鼠腹腔注射（IP）AMI后，给药后最初30分钟内脑组织浓度升高，随后下降。脑组织浓度随IP剂量的变化呈线性增加，随静脉剂量的变化呈对数增加。在急性给药的大鼠中，脑组织和血浆浓度之间不存在简单的关系。然而，在长期治疗的动物中，血浆和脑组织浓度之间存在线性关系（r = 0.96，P < 0.001）。在长期治疗的大鼠中观察到的脑：血浆药物比率与人类报道的比率一致。因此，从这些研究得出的结论可能可以外推到临床情况。根据我们的数据，治疗剂量下达到的药物摩尔浓度为10^(-5)-10^(-6) M。这些信息可能有助于理解通常以摩尔浓度报道的体外药物：受体结合研究的临床相关性。
