title: [Pharmacokinetics of 6beta-naltrexol after single and multiple intramuscular injections in Beagle dogs].
abstract: The pharmacokinetics of 6beta-naltrexol (6beta-NOL) following single intramuscular administration and multiple intramuscular injection once per day for seven days was studied in 4 Beagle dogs. Plasma concentration of 6beta-NOL in dogs was analyzed by a combination of high performance liquid chromatography (HPLC) and electrochemical detection with naloxone (NLX) as internal standard. After single intramuscular injection of 0.2 mg x kg(-1) 6beta-NOL, the plasma concentration-time curve of the drug was found to fit to a two compartment model with first-order absorption. The main parameters of single dosing were as follows: t1/2alpha was (0.26 +/- 0.23) h, t1/2beta was (4.77 +/- 1.65) h, C(max) was (81.65 +/- 5.61) ng x mL(-1), t(peak) was (0.27 +/- 0.07) h, CL(s) was (1.20 +/- 0.06) L x kg(-1) x h(-1), V/F(c) was (1.94 +/- 0.15) L x kg(-1), and AUC(0-t) was (166.82 +/- 7.68) ng x h x mL(-1), separately. After multiple intramuscular injection of 0.2 mg x kg(-1) 6beta-NOL once per day for seven days, the plasma concentration-time curve of the drug fitted to a two compartment model with first-order absorption too. The main parameters of the last dosing were as follows: t1/2alpha was (0.19 +/- 0.18) h, t1/2beta was (5.79 +/- 1.50) h, C(max) was (79.82 +/- 10.5) ng x mL(-1), t(peak) was (0.18 +/- 0.08) h, CL(s) was (1.12 +/- 0.07) L x kg(-1) x h(-1), V/F(c) was (2.10 +/- 0.27) L x kg(-1), and AUC(0-t) was (173.23 +/- 9.49) ng x h x mL(-1), separately. The difference of the parameters between the first and the last dosing was not significant, showing that the plasma kinetics of 6beta-naltrexol was not changed after multiple administrations. In the course of multiple administration, the peak and valley concentration of plasma 6beta-naltrexol were (79.03 +/- 10.3) and (1.50 +/- 0.93) ng x mL(-1), respectively. No clear adverse events were noted during this study. These results showed that plasma 6beta-naltrexol fits to a two compartment model with first-order absorption in dog after intramuscular administration and their pharmacokinetic parameters were reported. There was no remarkable change on plasma pharmacokinetics of 6beta-naltrexol after multiple intramuscular administrations.
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Ling-Di
authors.initials: LD
authors.lastname: Yan
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Hua-Jin
authors.initials: HJ
authors.lastname: Dong
authors.forename: Meng-Xun
authors.initials: MX
authors.lastname: Cui
authors.forename: Xia-Jun
authors.initials: XJ
authors.lastname: Yao
authors.forename: Yong-Shao
authors.initials: YS
authors.lastname: Liu
authors.forename: Zheng-Hua
authors.initials: ZH
authors.lastname: Gong
authors.forename: Ze-Hui
authors.initials: ZH
authors.lastname: Gong
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006207:Half-Life; D007273:Injections, Intramuscular; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: C010410:6 beta-hydroxynaltrexone; D009271:Naltrexone