EFFECT OF NIFEDIPINE ON THE ELIMINATION OF THEOPHYLLINE IN THE RABBITSUBJECTED TO HYPOXIA OR TO AN INFLAMMATORY REACTION

This study was performed to assess whether nifedipine could prevent th e decrease in hepatic cytochrome P450 induced by acute moderate hypoxi a or an inflammatory reaction. Rabbits were subjected to acute moderat e hypoxia (PaO2 much greater than 37 mmHg), with or without pretreatme nt with nifedipine (0.5 mg kg(-1) subcutaneously every 8 h, for 48 h). Another group received 5 mL of turpentine subcutaneously with or with out pretreatment with nifedipine (0.5 mg kg(-1) s.c. every 8 h, for 72 h). The kinetics of 2.5 mg kg(-1) of theophylline were studied in all rabbits up to 8 h, at which time total cytochrome P450 and malondiald ehyde were assessed in the liver. Compared with control rabbits, hypox ia and an inflammatory reaction increased theophylline plasma concentr ations, as a result of a decrease in theophylline systemic clearance. Both experimental conditions reduced hepatic cytochrome P450 by 40 to 50% and increased hepatic malondialdehyde by approximately 50% (P < 0. 05). In control animals, pretreatment with nifedipine did not influenc e theophylline kinetics, the liver content in cytochrome P450 or malon dialdehyde. Pretreatment with nifedipine partially prevented the hypox ia- and the inflammation-induced decrease in liver cytochrome P450; ho wever, nifedipine did not prevent the decrease in theophylline clearan ce or the increase in liver malondialdehyde. It is concluded that nife dipine affords a partial protection against hypoxia- or inflammation-i nduced hepatic cellular injury.