氨酚待因2号片的药代动力学及其相对生物利用度的研究

氨酚待因2号片是一改进的解热镇痛复方药,其中含扑热息痛300 mg/片,磷酸可待因15 mg/片。作为新的复方药,有必要对其药代动力学进行研究。本文用原料药配成水剂与片剂对比,计算相对生物利用度。用HPLC和GC-MS法分别检测了8位正常健康志愿者一次po氨酚待因2号片剂或水剂(30 mg磷酸可待因和600mg扑热息痛)后血浆中可待因和扑热息痛的含量。结果如下:po两片氨酚待因2号片后,扑热息痛的药代动力学符合二室模型;t_(peak)=0.74 h±s 0.43 h,C_(max)=8.04 mg·L~(-1)±s 3.96 mg·L~(-1),t_(1/2)=2.81 h±s1.09 h,Clr=0.39 L·h~(-1)±s 0.12 L·h~(-1),Cls=30.77 L·h~(-1)±s 9.02 L·h~(-1)。氨酚待因片中的可待因的药代动力学符合二室模型;t_(peak)=0.87 h±s 0.15 h,C_(max)=50.65μg·L~(-1)±s10.17μg·L~(-1),t_(1/2)=3.11h±s 0.49h,Clr=16.12L·h~(-1)±s 2.02L·h~(-1),Cls=173L·h~(-1)±s 11.40 L·h~(-1);po水剂对照药后,扑热息痛和可待因的药代动力学房室模型均与po片剂的药代规律相似,统计学上无显著差异(P>0.05)。扑热息痛和可待因的相对生物度分别为99.97％±s 10.55％,100.73％±s 7.85％。

THE PHARMACOKINETICS OF No 2 ACETAMINOPHEN-CODEINE COMPOUND TABLET IN NORMAL VOLUNTEERS

A comparative pharmacokinetics between tablet and solution of acetaminophen - codeine compound (cotaining 300 mg acetaminophen and 15 mg codeine in each tablet ) was carried out in 8 male volunteers. Each man was given two tablets or the solution of combination of the same dosage of codeine and acetaminophen after an over night fasting. The samples of the plasma and urine were collected, and detected by HPLC for acetaminophen and GC - MS for codeine. The results were as follows: 1. the drug level-time of acetaminophen and codeine are fitted to two open - compartment model. The parameters of acetaminophen were: tpeak=0.74 h±s 0.43h, Cmax = 8.04 mg · L-1 ± s 3. 96 mg · L-1, t1/2β = 2.81 h±s 1.09 h, Clr = 0.39 L · h-1±s 0.12 L · h-1, Cls =30.77 L · h-1±s 9.02 h · L-1. The parameters of codeine were: tpeak=0.87 h ± s 0.15 h, Gmax= 0. 65 μug · L-1 ± s 10.17 μg · L-1, t1/2β= 3. 11 h ±s 0.49 h, Clr = 16. 12 L · h-1±s 2. 02 L · h-1, Cls = 173 L · h-1 ± s 11.40 L · h-1; 2. the drug level-time of acetaminophen and codeine of solution are also fitted to two open - compartment model. Their pharmacokinetic parameters was all similiar to those of drugs in tablet. The relative bioavailability of acetaminophen and codeine was 99.97% ±s 10.55% and 100.73% ±s 7.85% respectively.