The impact of acute phase response on the plasma clearance of antipyrine, theophylline, phenytoin and nifedipine in rabbits

The impact of acute phase response (APR) on the plasma clearances of antipy rine, theophylline, phenytoin and nifedipine was studied using 50 female ra bbits, APR was induced by a bolus intramuscular injection of Escherichia co li lipopolysaccharide (LPS, 50 mug/kg). No abnormal findings, other than an increase in rectal body temperature and the plasma concentration of interl eukin-6 (IL-6), were observed in the LPS-treated animals. Twenty-four hours after LPS injection, the pharmacokinetic parameters of the four drugs were obtained following intravenous administrations of antipyrine (7 mg/kg), th eophylline (5 mg/kg), phenytoin (10 mg/kg) and nifedipine (1 mg/kg). Total body clearances of antipyrine, theophylline, phenytoin and nifedipine in LP S-treated rabbits decreased, and terminal elimination half-life and the mea n residence time of these drugs increased compared with those in the contro l rabbits. The apparent volume of distribution for phenytoin and nifedipine increased after the LPS injection, although the binding percentage of the drugs with plasma protein did not change. These results suggested that APR appears to decrease the plasma clearances of these drugs in rabbits, which may be due to the suppression of the activity of cytochrome P450 enzymes.