Kinetics of pyrimethamine in young and adult rats on a standard diet and on a low-protein diet

A pharmacokinetic study of pyrimethamine was carried out in 4- (103–115 g) and 12-week old (260–280 g) white male Wistar rats fed a standard diet containing 24% protein, and a low-protein diet containing 8% protein. After intragastric administration of the drug in a single dose of 40 mg/kg body weight, the concentrations of pyrimethamine in the blood were determined at different time points from 15 min to 20 hours post-dose. On the basis of the results obtained, a number of parameters characterizing the course of absorption and elimination of the drug from the blood were calculated. The majority of parameters were dependent on both age and type of diet. The greatest bioavailability was observed in the 4-week old rats: for the animals fed the low-protein diet, the area under the concentration — time curve (AUC) amounted to 593.0 and for those on the standard diet the AUC was 503.1. In the older rats, this parameter was 339.3 and 228.1 respectively. The ke values were lower in the younger rats (i.e. 0.0121 h−1 and 0.0135 h−1) than in the older animals (i.e. 0.0164 h−1 and 0.0193 h−1 respectively). The elimination half-life (t1/2) was higher in the 4-week old rats (i.e. 57.1 h; 8% protein, and 51.2 h; 24% protein) than in the 12-week old animals (i.e. 42.4 h; 8% protein, and 36.0 h; 24% protein).