title: The relationship between the pharmacological effect of amitriptyline based on an improved forced-swimming test and plasma concentration in rats.
abstract: The relationship between the plasma concentration of amitriptyline (AMI) and its pharmacological effect was investigated in rats. The plasma concentration of AMI was maintained constantly from 5 h to 7 d after intraperitoneal infusion by the implantation of an osmotic minipump with an adjusted release rate of 20 mg/kg/d of AMI. Neither the plasma or brain concentrations of AMI in a 24-h infusion group were significantly different as compared with those in the 7-d group. The pharmacological effect of AMI was measured by our improved forced-swimming test. When AMI (dose of 20 and 50 mg/kg/d) was infused, the pharmacological effect in both infusion groups of rats was increased significantly at each dose in comparison to that of the control rats (p < 0.05). With 10 mg/kg/d infusion, the effect in the 7-d group increased significantly as compared with that of the control (p < 0.05), although the effect in the 24-h group did not change. The effect was increased in both groups with an increase of dose. When the effect was plotted to the area under the plasma concentration-time curve (AUC), the effect approached a limiting value (12 micrograms/ml.h). Therefore, it was suggested that 12 micrograms.ml/h as the AUC for AMI was enough to obtain a maximum AMI pharmacological effect in rats. From these results, we concluded that the AUC for AMI may be a useful index to evaluate its pharmacological effect, rather than the plasma concentration.
authors.affiliation: Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Ohshima
authors.forename: H
authors.initials: H
authors.lastname: Kotaki
authors.forename: Y
authors.initials: Y
authors.lastname: Sawada
authors.forename: T
authors.initials: T
authors.lastname: Iga
mesh_terms: D000639:Amitriptyline / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000097:blood / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004343:Drug Implants; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009961:Orosomucoid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D004343:Drug Implants; D009961:Orosomucoid; D012709:Serum Albumin; D000639:Amitriptyline