Castañeda-Hernández G, Favari L, Hoyo-Vadillo C
Departamento de Farmcología y Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
Arzneimittelforschung. 1995 May;45(5):585-9.
The relationship between the plasma concentration and the anti-inflammatory effect of naproxen (CAS 22204-53-1) after oral administration of a 6 mg.kg-1 dose was studied in rats with galactosamine-induced acute hepatitis and under control conditions. In control animals naproxen peak plasma levels of 35 +/- 0.4 micrograms.ml-1 were reached in 0.5 +/- 0 h. Concentration then decayed, half-life being 5.2 +/- 0.4 h. AUC was 131 +/- 5 micrograms.h.ml-1. In intoxicated rats peak plasma levels of 29 +/- 0.3 micrograms.ml-1 were reached in 0.7 +/- 0.1 h, half-life was increased to 11.1 +/- 1.3 h, and the AUC reached 259 +/- 21 micrograms.h.ml-1. In control rats the protective effect of naproxen against carrageenan-induced inflammation increased slowly, reaching a maximum of 38% in 4 h. The protective effect against plasma concentration curve exhibited a clear counterclockwise hysteresis, probably due to a slow naproxen transport from the circulation to its site of action. In animals with hepatitis, the protective effect remained quite constant at about 40% despite variations in plasma levels, probably because the maximal effect was reached. No clear hysteresis was observed in the effect-plasma concentration curve, suggesting that naproxen arrival to its site of action was faster. Results show that the relationship between naproxen plasma concentration and its anti-inflammatory effect is complex and therefore predictions on the pharmacological response in liver damage cannot be readily made by solely considering pharmacokinetic data.
在给予6 mg.kg-1剂量萘普生（CAS 22204-53-1）口服后，研究了其血浆浓度与抗炎作用之间的关系，实验对象为半乳糖胺诱导的急性肝炎大鼠以及处于对照条件下的大鼠。在对照动物中，萘普生的血浆峰值水平在0.5±0小时达到35±0.4微克/毫升。随后浓度下降，半衰期为5.2±0.4小时。曲线下面积（AUC）为131±5微克·小时/毫升。在中毒大鼠中，血浆峰值水平在0.7±0.1小时达到29±0.3微克/毫升，半衰期增加到11.1±1.3小时，AUC达到259±21微克·小时/毫升。在对照大鼠中，萘普生对角叉菜胶诱导的炎症的保护作用缓慢增加，在4小时内达到最大值38%。保护作用与血浆浓度曲线呈现明显的逆时针滞后现象，这可能是由于萘普生从循环系统转运到其作用部位的过程缓慢。在患有肝炎的动物中，尽管血浆水平有所变化，但保护作用在约40%处保持相当稳定，可能是因为已达到最大效应。在效应-血浆浓度曲线中未观察到明显的滞后现象，这表明萘普生到达其作用部位的速度更快。结果表明，萘普生血浆浓度与其抗炎作用之间的关系较为复杂，因此不能仅通过考虑药代动力学数据就轻易预测肝损伤中的药理反应。
