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目的建立格列齐特血药浓度的高效液相色谱测定方法,研究Beagle犬单、多剂量口服格列齐特渗透泵片的药动学。方法用HPLC法测定6只健康Beagle犬单剂量和多剂量口服格列齐特缓释片和渗透泵片的血药浓度,以DAS2.0软件计算药动学参数。结果格列齐特的药-时曲线符合单室模型。单剂量给药后,缓释片和渗透泵片的t1/2分别为(6.0±s1.6)h和(7.4±2.3)h,tmax分别为(8.0±2.5)h和(6.2±2.9)h,ρmax分别为(8.1±3.2)mg·L-1和(6.6±1.6)mg·L-1,AUC0～∞分别为(146±8)mg·h·L-1和(144±17)mg·h·L-1,渗透泵片的相对生物利用度为(99±15)%。多剂量给药后,缓释片和渗透泵片的t1/2分别为(8.0±2.5)h和(9±3)h,tmax分别为(4.2±0.4)h和(5.3±0.5)h,ρmax分别为(14.4±1.8)mg·L-1和(12.5±1.7)mg·L-1,ρmin分别为(4.1±1.5)mg·L-1和(5.8±1.5)mg·L-1,ρav分别为(10.2±1.1)mg·L-1和(11.0±1.2)mg·L-1,AUC0～∞分别为(263±29)mg·h·L-1和(270±31)mg·h·L-1,DF分别为(103±21)%和(61±26)%。渗透泵片的相对生物利用度为(103±9)%。结论本方法准确、灵敏,格列齐特在犬体内的药动学符合单室模型,2种片剂生物等效。
OBJECTIVE To establish a HPLC method for the determination of gliclazide in plasma and to study the pharmacokinetics of Beagle dogs with single and multiple doses of oral gliclazide. Methods The plasma concentrations of single and multiple doses of oral glicachet and osmotic pump tablets in 6 healthy Beagle dogs were determined by HPLC. The pharmacokinetic parameters were calculated by DAS2.0 software. Results The drug-time curve of Gliclazide conformed to the single-compartment model. After single-dose administration, the t1 / 2 of sustained release tablets and osmotic pump tablets were (6.0 ± s1.6) h and (7.4 ± 2.3) h, respectively, with tmax of (8.0 ± 2.5) h and (6.2 ± 2.9) h and ρmax were (8.1 ± 3.2) mg · L-1 and (6.6 ± 1.6) mg · L-1, and the AUC0 ~ ∞ were (146 ± 8) mg · h · L-1 and (144 ± 17) mg · h · L-1. The relative bioavailability of osmotic pump tablets was (99 ± 15)%. After multiple dose administration, the t1 / 2 of the sustained-release tablets and the osmotic pump tablets were (8.0 ± 2.5) h and (9 ± 3) h, respectively, and the tmax were (4.2 ± 0.4) h and (5.3 ± 0.5) ρmax were (14.4 ± 1.8) mg · L-1 and (12.5 ± 1.7) mg · L-1, respectively, and ρmin were (4.1 ± 1.5) mg · L-1 and (5.8 ± 1.5) mg · L- ρav were (10.2 ± 1.1) mg · L-1 and (11.0 ± 1.2) mg · L-1, respectively, and AUC0 ~ ∞ were (263 ± 29) mg · h · L-1 and (270 ± 31) mg · h · L-1 and DF were (103 ± 21)% and (61 ± 26)%, respectively. The relative bioavailability of osmotic pump tablets was (103 ± 9)%. Conclusion The method is accurate and sensitive. The pharmacokinetics of Gliclazide in canines accorded with single-compartment model and bioavailability of two kinds of tablets.