Chindavijak B, Belpaire F M, Bogaert M G
Heymans Institute of Pharmacology, University of Gent Medical School, Gent, Belgium.
J Pharm Pharmacol. 1987 Dec;39(12):997-1002. doi: 10.1111/j.2042-7158.1987.tb03147.x.
The effect of inflammation, induced in rats by injection of turpentine oil, on drug disposition has been evaluated in rat isolated perfused livers. The drugs studied were a low extraction drug, antipyrine, and two high extraction drugs, lignocaine and propranolol. Turpentine significantly increased the half-life of antipyrine and of propranolol, but not that of lignocaine. Proadifen (SKF 525A) significantly increased the half-life of all three drugs. Turpentine decreased the clearance of antipyrine significantly by about 50% and that of propranolol non-significantly by about 20%, but did not affect the clearance of lignocaine. Proadifen significantly decreased the clearance of all three drugs, but this was most pronounced for antipyrine. In both turpentine- and proadifen-treated rats a significant increase in volume of distribution of propranolol was observed. The results show that, as with proadifen, turpentine-induced inflammation affects the hepatic clearance of antipyrine in the rat isolated perfused liver. With both high extraction drugs, the effect of inflammation on their clearance was low or absent, in contrast to the effect of proadifen. This suggests that a possible effect of inflammation on intrinsic clearance is not large enough to influence the hepatic clearance of the high extraction drugs.
通过给大鼠注射松节油诱导炎症，研究了炎症对大鼠离体灌流肝脏中药物处置的影响。所研究的药物有低摄取药物安替比林，以及两种高摄取药物利多卡因和普萘洛尔。松节油显著延长了安替比林和普萘洛尔的半衰期，但未延长利多卡因的半衰期。丙磺舒（SKF 525A）显著延长了这三种药物的半衰期。松节油使安替比林的清除率显著降低约50%，使普萘洛尔的清除率非显著降低约20%，但未影响利多卡因的清除率。丙磺舒显著降低了这三种药物的清除率，但对安替比林的影响最为明显。在松节油和丙磺舒处理的大鼠中，均观察到普萘洛尔的分布容积显著增加。结果表明，与丙磺舒一样，松节油诱导的炎症会影响大鼠离体灌流肝脏中安替比林的肝清除率。与丙磺舒的作用相反，对于两种高摄取药物，炎症对其清除率的影响较小或无影响。这表明炎症对内在清除率的可能影响不足以影响高摄取药物的肝清除率。
