Illum L, Hinchcliffe M, Davis S S
West Pharmaceutical Services, Drug Delivery and Clinical Research Centre Ltd., Albert Einstein Centre, Nottingham Science and Technology Park, Nottingham NG7 2TN, United Kingdom.
Pharm Res. 2003 Sep;20(9):1474-84. doi: 10.1023/a:1025722614154.
Investigate the effect of blood sampling site and physicochemical characteristics of drugs on the pharmacokinetic (PK) parameters obtained after intravenous and nasal administration in sheep and compare results with computer simulations.
Three drugs, insulin, morphine, and nicotine, were administered nasally and by intravenous (IV) injection to sheep, and serial blood samples collected concurrently from the carotid artery (insulin, morphine) or cephalic vein (nicotine) and jugular vein. Plasma drug concentrations were measured, and pharmacokinetic and statistical analyses performed, to evaluate sampling site differences.
After nasal insulin, bioavailabilities calculated from the two blood sampling site data were comparable. In contrast, apparent bioavailabilities following nasal morphine or nicotine were significantly higher when sampling was from the jugular vein. These results were supported by computer simulations. These observations are attributed to the greater effects of noninstantaneous mixing of drugs for jugular vein sampling following nasal dosing, compared to the other sampling sites, which is significant for drugs that are rapidly and well absorbed and that have a high volume of distribution (Vd).
The results clearly show that the characteristics of the drug and the blood sampling site can have a significant effect on the pharmacokinetic results obtained after nasal administration in sheep.
研究采血部位和药物理化特性对绵羊静脉注射和鼻腔给药后获得的药代动力学（PK）参数的影响，并将结果与计算机模拟结果进行比较。
将胰岛素、吗啡和尼古丁三种药物经鼻腔和静脉注射给予绵羊，并同时从颈动脉（胰岛素、吗啡）或头静脉（尼古丁）和颈静脉采集系列血样。测定血浆药物浓度，并进行药代动力学和统计分析，以评估采血部位差异。
鼻腔给予胰岛素后，根据两个采血部位数据计算的生物利用度相当。相比之下，鼻腔给予吗啡或尼古丁后，从颈静脉采血时的表观生物利用度显著更高。这些结果得到了计算机模拟的支持。这些观察结果归因于鼻腔给药后颈静脉采血时药物非瞬时混合的影响比其他采血部位更大，这对于吸收迅速且良好且分布容积（Vd）高的药物具有重要意义。
结果清楚地表明，药物特性和采血部位可对绵羊鼻腔给药后获得的药代动力学结果产生显著影响。
