Population pharmacokinetic analysis of the active product of dipyrone.

ABSTRACT

OBJECTIVE: Pharmacokinetics of 4-methyl-amino-antipyrine (MAA), the active metabolite of the nonsteroidal anti-inflammatory agent dipyrone, whose time course correlates to the therapeutic effect of the drug, are studied. STUDY DESIGN AND SETTING: 153 patients hospitalized in the Department of Medicine at the Hadassah University Hospital, Jerusalem, Israel. INTERVENTION Patients receiving dipyrone for the treatment of fever or pain were asked to participate in the study. Pharmacokinetics and statistical analysis: Using the population approach based on a formerly developed experimental model, the relationships between pharmacokinetic parameters and demographic and physiological covariates are explored. RESULTS: The results of the analysis show considerable variability in pharmacokinetics across the study population, and a significant decrease in clearance with age. CONCLUSION: A population pharmacokinetic analysis of MAA, the active product of dipyrone, reveals that age is a significant predictor of MAA disposition. Covariates that measure hepatic and renal function do not appear to be good predictors of the rate of MAA disposition.