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目的评价中国男性志愿者口服3种左旋多巴给药方案后的人体稳态药动学和生物等效性。方法采用液相色谱-质谱/质谱法测定18名健康受试者口服3种左旋多巴制剂后血浆中的左旋多巴浓度。采用WinNonlin药动软件计算药动学参数,并评价其生物等效性。结果卡左双多巴控释片+恩他卡朋片(测试药1)、多巴丝肼片+恩他卡朋片(测试药2)和卡左双多巴控释片(参比药)的左旋多巴药动学参数AUC0-12分别为(3 657.57±683.27)、(2 365.87±597.81)和(3 017.48±612.99)ng.h.mL-1,实测ρmax为(809.56±128.40)、(742.50±152.81)和(746.83±148.53)ng.mL-1,实测tmax为(2.53±0.50)、(1.42±0.70)和(2.19±0.71)h,MRT0-inf为(6.57±2.15)、(6.04±1.91)和(6.75±2.80)h,t1/2为(2.96±1.04)、(2.72±1.43)和(2.87±1.12)h。以左旋多巴计,测试药1和测试药2与参比药的相对生物利用度分别为(128.77±47.69)%和(80.43±20.11)%。结论经统计学分析,以左旋多巴计,测试药1、测试药2分别和参比药相比均生物不等效。测试药1、测试药2与参比药的ρmax均生物等效。经非参数秩和检验,与参比药相比,测试药1的tmax无显著差异(P>0.05),测试药2有显著差异(P<0.05),参比药tmax大于测试药2的tmax。
Objective To evaluate the steady state pharmacokinetics and bioequivalence of oral levodopa in Chinese male volunteers. Methods The concentrations of levodopa in plasma of 18 healthy volunteers after oral administration of 3 levodopa preparations were determined by liquid chromatography-mass spectrometry / mass spectrometry. Pharmacokinetic parameters were calculated using WinNonlin’s pharmacokinetic software and their bioequivalence was evaluated. RESULTS Card ZDDT + ntocapain (test drug 1), DOPS hydrate + entacapone (test drug 2) and card ZDZD (reference drug ) Of levodopa pharmacokinetic parameters AUC0-12 were (3 657.57 ± 683.27), (2 365.87 ± 597.81) and (3 017.48 ± 612.99) ng.h.mL-1, the measured ρmax was (809.56 ± 128.40) , (742.50 ± 152.81) and (746.83 ± 148.53) ng.mL-1 respectively. The tmax was (2.53 ± 0.50), (1.42 ± 0.70) and (2.19 ± 0.71) (6.04 ± 1.91) and (6.75 ± 2.80) h, t1 / 2 were (2.96 ± 1.04), (2.72 ± 1.43) and (2.87 ± 1.12) h, respectively. The relative bioavailability of test drug 1, test drug 2 and reference drug were (128.77 ± 47.69)% and (80.43 ± 20.11)%, respectively, based on levodopa. Conclusions According to statistical analysis, levodopa, test drug 1 and test drug 2 are not bioequivalent to reference drugs, respectively. Test drug 1, test drug 2 and reference drug ρ max are bioequivalent. Compared with the reference drug, the tmax of the test drug 1 was not significantly different (P> 0.05), the test drug 2 was significantly different (P <0.05), and the reference drug tmax was greater than that of the test drug 2 .