Pyrazinamide pharmacokinetics and efficacy in adults and children

SummaryPyrazinamide (PZA) is an essential sterilizing drug and with rifampicin enables six-month short-course antituberculosis chemotherapy. Despite routine use for nearly forty years uncertainty remains regarding the most appropriate PZA dosage for children. In view of this uncertainty literature relating to the efficacy and pharmacokinetics of PZA in children treated for tuberculosis and in adult volunteers and patients was reviewed. Making use of the PZA maximum concentration (Cmax) following various PZA dosages in different groups straight line regression of concentration on dosage was fitted through the origin by least squares and weighted for the numbers of subjects. The fitted line offers an approximation of the likely PZA Cmax that would result from a particular dosage. The slopes of Cmax/dosage of the fitted lines are 1.32 (SE 0.099) for paediatric patients, 1.36 (SE 0.051) for adult volunteers and 1.35 (SE 0.037) for adult patients; there is little difference between the Cmax concentrations achieved in children and adults, whether patients or healthy volunteers, following various mg/kg body weight dosages, suggesting that children and adults receiving the same mg/kg body weight PZA dosage will reach a similar Cmax. Children can receive the same mg/kg body weight PZA dosage as adults.

► The literature describing the pharmacokinetics of PZA in children and adults is reviewed.
► The maximum serum concentrations of PZA reached in children following a range of dosages are compared to those reached in adults after the same dosages.
► The slopes of Cmax/dosage for paediatric patients (1.32; SE 0.099), adult volunteers (1.36; SE 0.037) and adult patients (1.35; SE 0.051) did not differ.
► Children receiving the same PZA dosage as adults will reach similar PZA serum concentrations.