中国临床药学杂志
中國臨床藥學雜誌
중국림상약학잡지
CHINESE JOURNAL OF CLINICAL PHARMACY
2005年
6期
327-331
,共5页
李雪宁%陈伟力%徐红蓉%李志善
李雪寧%陳偉力%徐紅蓉%李誌善
리설저%진위력%서홍용%리지선
甲氯噻嗪%LC-MS/MS法%药动学
甲氯噻嗪%LC-MS/MS法%藥動學
갑록새진%LC-MS/MS법%약동학
methyclothiazide%LC-MS/MS%pharmacokinetics
目的为了获得国产甲氯噻嗪在中国人体内的代谢情况,以便指导临床合理用药,对国产的甲氯噻嗪片在健康中国男性受试者中空腹单剂量口服不同剂量时的药动学特点进行评价.方法采用LC-MS/MS法测定血浆中甲氯噻嗪的浓度并用非房室模型计算药动学参数.结果入选的10名受试者单剂量口服3种不同剂量(2.5、5.0和10 mg)的甲氯噻嗪后的AUC0→t分别为:(128.40±20.88)、(257.68±37.10)和(517.27±119.17)μg·h·L-1;AUC0→∞分别为:(150.47±24.78)、(299.52±45.56)和(602.57±129.67)μg·h·L-1;cmax分别为(8.43±2.21)、(16.60±2.53)和(32.08±8.44)μg·L-1;tmax分别为(2.60±0.70)、(2.30±0.95)和(3.25±1.27)h;T1/2分别为(17.63±2.61)、(17.37±2.62)和(17.87±2.49)h;Ka分别为(1.195±0.720)、(1.352±0.626)和(1.221±1.152)h-1;Ke分别为(0.034 4±0.105)、(0.039 1±0.010 3)和(0.036 2±0.008 1)h-1;Vd分别为(236.36±69.20)、(221.79±87.94)和(299.30±204.72)L;CL分别为(0.0174±0.0039)、(0.0178±0.0035)和(0.0179±0.0036)L·h-1.结论 AUC0→t(r=1)和cmax(r=0.999 8)在2.5～10 mg范围内呈良好的线性关系.tmax和T1/2经ANOVA(SPSS 10.0)统计学处理3种不同剂量间差别无统计学意义.剂量校正后AUC0→t和cmax的几何均数分别是:50.69、51.04、50.39μg·h·L-1和3.26、3.28、3.06μg·L-1,其值基本相近.
目的為瞭穫得國產甲氯噻嗪在中國人體內的代謝情況,以便指導臨床閤理用藥,對國產的甲氯噻嗪片在健康中國男性受試者中空腹單劑量口服不同劑量時的藥動學特點進行評價.方法採用LC-MS/MS法測定血漿中甲氯噻嗪的濃度併用非房室模型計算藥動學參數.結果入選的10名受試者單劑量口服3種不同劑量(2.5、5.0和10 mg)的甲氯噻嗪後的AUC0→t分彆為:(128.40±20.88)、(257.68±37.10)和(517.27±119.17)μg·h·L-1;AUC0→∞分彆為:(150.47±24.78)、(299.52±45.56)和(602.57±129.67)μg·h·L-1;cmax分彆為(8.43±2.21)、(16.60±2.53)和(32.08±8.44)μg·L-1;tmax分彆為(2.60±0.70)、(2.30±0.95)和(3.25±1.27)h;T1/2分彆為(17.63±2.61)、(17.37±2.62)和(17.87±2.49)h;Ka分彆為(1.195±0.720)、(1.352±0.626)和(1.221±1.152)h-1;Ke分彆為(0.034 4±0.105)、(0.039 1±0.010 3)和(0.036 2±0.008 1)h-1;Vd分彆為(236.36±69.20)、(221.79±87.94)和(299.30±204.72)L;CL分彆為(0.0174±0.0039)、(0.0178±0.0035)和(0.0179±0.0036)L·h-1.結論 AUC0→t(r=1)和cmax(r=0.999 8)在2.5～10 mg範圍內呈良好的線性關繫.tmax和T1/2經ANOVA(SPSS 10.0)統計學處理3種不同劑量間差彆無統計學意義.劑量校正後AUC0→t和cmax的幾何均數分彆是:50.69、51.04、50.39μg·h·L-1和3.26、3.28、3.06μg·L-1,其值基本相近.
목적위료획득국산갑록새진재중국인체내적대사정황,이편지도림상합리용약,대국산적갑록새진편재건강중국남성수시자중공복단제량구복불동제량시적약동학특점진행평개.방법채용LC-MS/MS법측정혈장중갑록새진적농도병용비방실모형계산약동학삼수.결과입선적10명수시자단제량구복3충불동제량(2.5、5.0화10 mg)적갑록새진후적AUC0→t분별위:(128.40±20.88)、(257.68±37.10)화(517.27±119.17)μg·h·L-1;AUC0→∞분별위:(150.47±24.78)、(299.52±45.56)화(602.57±129.67)μg·h·L-1;cmax분별위(8.43±2.21)、(16.60±2.53)화(32.08±8.44)μg·L-1;tmax분별위(2.60±0.70)、(2.30±0.95)화(3.25±1.27)h;T1/2분별위(17.63±2.61)、(17.37±2.62)화(17.87±2.49)h;Ka분별위(1.195±0.720)、(1.352±0.626)화(1.221±1.152)h-1;Ke분별위(0.034 4±0.105)、(0.039 1±0.010 3)화(0.036 2±0.008 1)h-1;Vd분별위(236.36±69.20)、(221.79±87.94)화(299.30±204.72)L;CL분별위(0.0174±0.0039)、(0.0178±0.0035)화(0.0179±0.0036)L·h-1.결론 AUC0→t(r=1)화cmax(r=0.999 8)재2.5～10 mg범위내정량호적선성관계.tmax화T1/2경ANOVA(SPSS 10.0)통계학처리3충불동제량간차별무통계학의의.제량교정후AUC0→t화cmax적궤하균수분별시:50.69、51.04、50.39μg·h·L-1화3.26、3.28、3.06μg·L-1,기치기본상근.
AIM To evaluate the safety and pharmacokinetic parameters of a domestic methyclothiazide tablet in Chinese healthy male volunteers after administered three different oral dosage. METHODS Ten healthy Chinese volunteers were given a different single oral dosage domestic methyclothiazide tablet. The concentration of methyclothiazide in blood plasma was measured by an validated LC-MS/MS method and were assessed with non-compartment model to obtain the pharmacokinetic parameters. RESULTS The pharmacokinetic parameters of methyclothiazide tablet for orally administered different dosage (2.5,5.0,10mg) were as follows: AUC0→t: (128.40 ± 20.88), (257.68 ± 37.10) and (517.27 ±119.17)μg·h· L-1; AUC0→∞: (150.47 ± 24.78), (299.52 ± 45.56) and (602.57 ± 129.67)μg· h·L-1; cmax:(8.43 ± 2.21) ,(16.60±2.53) and (32.08 ± 8.44)μg·L-1; tmax:(2.60 ± 0.70) ,(2.30 ± 0.95) and (3.25 ± 1.27)h;T1/2:(17.63 ± 2.61), (17.37 ± 2.62) and (17.87 ± 2.49)h; Ka: (1. 195 ± 0.720), (1.352 ± 0.626) and(1.221± 1.152) h-1;Ke: (0.0344 ± 0.1050),(0.0391 ± 0.0103) and (0.0362 ±0.0081) h-1; Vd: (236.36 ±69.20), (221.79 ± 87.94) and (299.30 ± 204.72) L;CL: (0.0174 ± 0.0039), (0.0178 ± 0.0035) and (0.0179 ±0.0036) L· h-1. CONCLUSION The results show that there was a good linear in AUC0→t (r = 1 ) and cmax (r =0.999 8) in dosage range of 2.5-10 mg. There is no significant difference in tmax and T1/2 between three different dosage groups (SPSS 10.0). The geometric mean of AUC0→t and cmax after dose is rectified are 50.69,51.04,50.39 μg·h·L-1and 3.26,3.28,3.06 μg· L- 1, respectively. No any adverse drug reactions are found during the whole study.
