Development of Physiologically Based Pharmacokinetic Model for Pregabalin to Predict the Pharmacokinetics in Pediatric Patients with Renal Impairment and Adjust Dosage Regimens PBPK Model of Pregabalin in Pediatric Patients with Renal Impairment

Pregabalin (PGB) is widely used clinically; however, its pharmacokinetics (PK) has not been studied in pediatric patients with renal impairment (RI). To design optimized PGB regimens for pediatric patients with varying degrees of RI and predict exposure to PGB, physiologically based pharmacokinetic (PBPK) models of PGB were developed and verified, and its disposition was simulated in the healthy population and adults with RI. The simulated results from the PBPK models after single-dose and multi-dose administrations of PGB were consistent with the corresponding observed data based on the fold error values of less than 2. The area under curve ratios were 1.23 +/- 0.06, 2.02 +/- 0.10, 3.86 +/- 0.21, and 9.92 +/- 0.79 in pediatric patients with mild, moderate, severe, and end-stage RI, respectively. Based on the predictions for pediatric patients with moderate, severe, and end-stage RI, the maximum dose should not exceed 7, 3.5, and 1.4 mg/kg/day, respectively, among those weighing < 30 kg, and it should not exceed 5, 2.5, and 1 mg/kg/day, respectively, among those weighing > 30 kg. In conclusion, the developed PBPK model is a valuable tool for predicting PGB dosage for pediatric patients with RI. (C) 2021 Published by Elsevier Inc. on behalf of American Pharmacists Association.

Automated summary

A physiologically based pharmacokinetic (PBPK) model was developed to predict pregabalin (PGB) dosage for pediatric patients with renal impairment (RI). The model was validated and used to simulate the disposition of PGB in the healthy population and adults with RI. The results showed that the model accurately predicted the exposure to PGB in different populations and suggested optimal dosage regimens for pediatric patients with varying degrees of RI.