title: A single-center, randomized, open-label, dose-escalation study to evaluate the pharmacokinetics of tacrine analogue octahydrogenacridine succinate tablets in healthy Chinese subjects.
abstract: The objectives of the present study were to investigate the pharmacokinetics (PK) of tacrine analogue octahydrogenacridine (OHA) succinate tablets in healthy Chinese subjects. A single-center, randomized, open-label, dose-escalation study was conducted in 42 healthy Chinese subjects. Part I of the study (n=30, 16 male and 14 female) evaluated the PK profiles of OHA in healthy Chinese subjects (aged 18-45 years) after single and multiple doses of 2 mg, 4 mg and 8 mg. Part II (n=10) assessed food effect on PK characteristics of OHA. The 10 participants of 4 mg dose group in part I were given another single dose of 4 mg OHA under fed condition. Part III (n=12, 7 male and 5 female) investigate PK behavior of OHA in elderly (aged 65-75 years) Chinese healthy subjects. In Part I, following a single- and multiple-dose, octahydrogenacridine succinate was rapidly absorbed with a median t(max) of 0.67 to 1.00 h, and was eliminated with a mean t1/2 of 2.27 to 2.98 h in all dose groups and did not appear to be dose dependent. In Part II, there were no significant differences in Cmax, AUC0-tn or tmax between 4 mg single dose fasting group and fed group (p=0.257, 0.153, 0.098, respectively). In Part III, both in single-dose and multiple-dose treatment, the main PK parameters of OHA in the elderly healthy Chinese subjects showed no statistical difference with those of non-elderly group. All these results indicated that OHA might be a promising drug under development for Alzheimer's disease (AD) therapy.
authors.affiliation: Department of Pharmacy, Peking University First Hospital, Beijing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Junyu
authors.initials: J
authors.lastname: Xu
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.forename: Depu
authors.initials: D
authors.lastname: Wang
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
authors.forename: Yimin
authors.initials: Y
authors.lastname: Cui
mesh_terms: D000166:Acridines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy; D002681:China; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D012016:Reference Values; D013386:Succinates / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013607:Tablets; D013619:Tacrine / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000166:Acridines; D013386:Succinates; D013607:Tablets; D013619:Tacrine