Ahlin A, Adem A, Junthé T, Ohman G, Nybäck H
Department of Psychiatry and Psychology, Karolinska Hospital, Stockholm, Sweden.
Int Clin Psychopharmacol. 1992 Spring;7(1):29-36.
The pharmacokinetics of tetrahydroaminoacridine (THA) was studied in patients suffering from Alzheimer's dementia. Single doses of the drug were administered by intravenous (15 mg), oral (50 mg) and rectal routes (25 mg). Pharmacokinetic parameters were related to clinical and biochemical effects in patients who, in a separate study, participated in a clinical trial of oral THA. The bioavailability of THA was low and varied considerably between subjects. Clinical improvement and occurrence of elevated liver enzymes correlated positively with drug bioavailability. Acetyl and butyryl cholinesterase activities in the plasma did not change following THA administration. Rectally administered THA had a higher bioavailability than orally administered THA in three subjects who were given the drug by both routes. These results indicate that a clinical trial of rectal THA would be justified as this administration route may improve resorption and diminish first-pass metabolism of the drug in the liver compared with oral administration.
在患有阿尔茨海默病痴呆症的患者中研究了四氢氨基吖啶（THA）的药代动力学。通过静脉注射（15毫克）、口服（50毫克）和直肠给药（25毫克）给予单剂量的该药物。在另一项研究中参与口服THA临床试验的患者中，药代动力学参数与临床和生化效应相关。THA的生物利用度较低，且在受试者之间差异很大。临床改善和肝酶升高的发生与药物生物利用度呈正相关。给予THA后，血浆中的乙酰胆碱酯酶和丁酰胆碱酯酶活性没有变化。在三名通过两种途径给药的受试者中，直肠给药的THA比口服给药的THA具有更高的生物利用度。这些结果表明，直肠THA的临床试验是合理的，因为与口服给药相比，这种给药途径可能会改善药物的吸收并减少肝脏中的首过代谢。
