The influence of malnutrition on the oral pharmacokinetics of nimesulide in rats.

Abstract

Malnutrition is a health problem in Mexico. It has been established that malnutrition may produce important changes in the pharmacological response to drugs, since changes in the pharmacodynamics and pharmacokinetics may occur. It has been described that a reduction of plasma proteins and in hepatic enzymes may occur. Due to these changes, absorption, distribution and elimination of drugs can be modified. Nimesulide is a non-steroidal anti-inflammatory agent that is widely used. This drug is importantly bound to plasma proteins and is metabolized through cytochrome P-450, two systems that are altered in malnutrition. In order to establish if malnutrition can modify the pharmacokinetics of nimesulide, a comparison of pharmacokinetic parameters obtained in control and protein-calorie malnourished rats was carried out. Two groups of 7 rats were employed in this study. At 45 days of age, group 1 received a standard balanced diet for 4 weeks, whereas, group 2 received a low protein diet for the same period. Then, rats received an oral dose of 10 mg/kg nimesulide and blood samples were drawn at selected times for 12 hr. Nimesulide whole blood levels were determined by HPLC and the pharmacokinetic parameters; Cmax 1.18 +/- 0.13 and 1.03 +/- 0.10 microg/ml, tmax 5.25 +/- 1.03 and 7.48 +/- 1.09 h and AUC12h 8.64 +/- 1.19 and 8.27 +/- 0.85 microg x h/ml were obtained. We conclude that malnutrition does not modify the oral pharmacokinetics of nimesulide.