Scientific Publications by FDA Staff

Eur J Drug Metab Pharmacokinet 2017 Aug;42(4):601-10

Prediction of clearance, volume of distribution, and half-life of drugs in extremely low to low birth weight neonates: an allometric approach.

Mahmood I

BACKGROUND AND OBJECTIVES: More than 20 million infants worldwide (15.5 % of all births) are born with low birth weight. Low birth weight is associated with poor growth in childhood and a higher incidence of adult diseases, such as type 2 diabetes, hypertension and cardiovascular disease. The objective of this study was to evaluate the predictive performance of allometric models to predict clearance, volume of distribution, and half-life in extremely low to low birth weight neonates (<1 to 2.5 kg body weight). METHODS: Several allometric models were used to predict clearance (4 models), volume of distribution (2 models), and half-life (2 models) in extremely low to low birth weight neonates. From the literature, clearance, volume of distribution, and half-life values for 16 drugs for these neonates were obtained. The predictive performance of these allometric models was evaluated by comparing the predicted values of the aforementioned pharmacokinetic parameters with the observed pharmacokinetic parameters in an individual neonate. For the evaluation of the predictive performance of these allometric models, there were 16 drugs with 36 (n = 279), 34 (n = 261), and 31 (n = 197) weight groups for clearance, volume of distribution, and half-life, respectively. RESULTS: The prediction error of