Sanaka M, Koike Y, Yamamoto T, Mineshita S, Yamaoka S, Hirama S, Tanaka H, Kuyama Y, Yamanaka M
Department of Internal Medicine, School of Medicine, Teikyo University, Japan.
Int J Clin Pharmacol Ther. 1997 Nov;35(11):509-13.
The rate of paracetamol absorption represents gastric emptying rate (GER) of liquids. Thus, the liquid GER is assessed by conventional pharmacokinetic parameters such as the maximum concentration and the time to maximum concentration after oral administration of paracetamol. However, the conventional parameters are subject not only to the rate but also to the extent of absorption. For the reliable assessment of GER we have proposed a new parameter, the C0.5/C0.25 ratio, for the rate of paracetamol absorption without being affected by the extent of absorption. Of 15 healthy male volunteers, 9 orally received 10 mg/kg of paracetamol with 200 ml of water as the "normal" GER group, and the other 6 took 10 mg/kg of paracetamol with 200 ml of a liquid nutrient (200 kcal/200 ml), which delays GER, as the "delayed" GER group. Blood samples were obtained at t = 0 (pre-dose), 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, and 8.0 hours (post-dose). In each subject, GER was assessed by the conventional parameters, the C0.5/C0.25 ratio, and the Wagner-Nelson method which provides an accurate estimate of the drug absorption rate. Using the C0.5/C0.25 ratio and the Wagner-Nelson method we could more clearly differentiate the delayed GER group from the normal GER group than by using the conventional parameters. This suggests that the C0.5/C0.25 ratio and the Wagner-Nelson method may be more reliable than the conventional parameters in detecting a delay in GER. Further, it should be noted that the C0.5/C0.25 ratio can be calculated from only 2 blood samples while the Wagner-Nelson method requires repeated blood sampling.
对乙酰氨基酚的吸收速率代表液体的胃排空率(GER)。因此,液体GER通过常规药代动力学参数进行评估,如口服对乙酰氨基酚后的最大浓度和达到最大浓度的时间。然而,这些常规参数不仅受吸收速率的影响,还受吸收程度的影响。为了可靠地评估GER,我们提出了一个新参数,即C0.5/C0.25比值,用于对乙酰氨基酚的吸收速率,且不受吸收程度的影响。15名健康男性志愿者中,9人口服10mg/kg对乙酰氨基酚加200ml水作为“正常”GER组,另外6人服用10mg/kg对乙酰氨基酚加200ml液体营养剂(200千卡/200ml),该营养剂会延迟GER,作为“延迟”GER组。在给药前(t = 0)、给药后0.25、0.5、0.75、1.0、1.5、2.0、3.0、4.0、6.0和8.0小时采集血样。在每个受试者中,通过常规参数、C0.5/C0.25比值以及能准确估计药物吸收速率的Wagner-Nelson方法评估GER。与使用常规参数相比,使用C0.5/C0.25比值和Wagner-Nelson方法能更清晰地区分延迟GER组和正常GER组。这表明在检测GER延迟方面,C0.5/C0.25比值和Wagner-Nelson方法可能比常规参数更可靠。此外,应注意C0.5/C0.25比值仅可从两份血样计算得出,而Wagner-Nelson方法需要重复采血。