Effect of Growth and Development on Pharmacokinetics of Antipyrine in Swine

The aim of this study was to analyze the effect of growth and development on the pharmacokinetics of antipyrine in swine. Four animals of 16 days old were used for the study. Pharmacokinetic (PK) studies were performed at ages 16, 29, 58, 72, 116, 131, 146, 1 60, 191, 220 days to cover the different life stages of animals from birth to adulthood, after IV administration of 16 mg kg(-1) of antipyrine. Blood samples were obtained at 0.0, 1.0, 2.0, 4.0, 6.0, 8.0 and 12 h post-administration and serum concentrations of drug were determined by validated method. Pharmacokinetic parameters as elimination half-life (t(1/2 el)), Volume of distribution (VD) and Clearance (Cl), showed variations in different ages of the study groups. The model that best fit t(1/2el) was the sum of sines and cosines in the periods 204, 102 and 51 days. For Cl, it was at 204, 102, 68 and 51 days and for Vd, it occurred at 204, 102, 68 and 40 days. As t(1/2el) increased, there was a reduction in Cl and vise versa. To explain these variations, the presence of an endogenous biological rhythm is proposed where periods of rapid growth may affect elimination and metabolic rates. These observations could explain some of the interindividual variations in PK of certain drugs that are eliminated by oxidation reactions. These observations bring into manifestation the close relationship existing between physical growth and drug elimination. Periodic variations observed in the half-life time and metabolic clearance rate of antipyrine probably reflect biologic variations resulting from the existence of biological endogenous rhythms that are common properties of all living beings and perhaps, one of the factors that most influence interindividual variation