Pharmacokinetics of theophylline in protein-calorie malnutrition

The influence of protein-calorie malnutrition (PCM) on the disposition of theophylline was investigated in male Sprague-Dawley rats fed for four weeks on a 23 per cent (control) or 5 per cent (low) protein diet ad lib. Dietary protein deficiency led to a decrease in body weight gain, plasma proteins, albumin, microsomal proteins, and cytochrome P-450. After intravenous administration of aminophylline equivalent to 10 mg kg-1 theophylline, the average mean residence time (MRT) was 58 per cent higher in the protein-deficient rats, while the total plasma clearance (Cl) per kilogram of body weight and elimination rate constant (k) were decreased by 39 per cent and 45 per cent, respectively, when compared to rats on a normal protein diet. No significant difference was found in the two groups of animals with respect to the apparent steady-state volume of distribution (Vss). The present results suggest that the mechanism responsible for the observed pharmacokinetic changes in the protein-deficient rats is related to the reduced amount and/or activity of the hepatic mixed function oxidases.