Prediction of Pharmacokinetics of IDP-73152 in Humans Using Physiologically-Based Pharmacokinetics

Abstract

IDP-73152, a novel peptide deformylase inhibitor with an antibacterial effect against Gram-positive bacteria, is in phase I development. The objective of this study was to develop a physiologically-based pharmacokinetic model (PBPK) for IDP-73152 in animals, and to extend the model to humans. Biopharmaceutical properties of IDP-73152 are determined using in vitro/in vivo experimentations for the PBPK model. A transit model consisting of gastrointestinal segments is applied for an estimation of the intestinal absorption kinetics. The PBPK model of IDP-73152 in rats is able to appropriately predict the plasma concentration-time profiles after the administration of IDP-73152 at different doses and by different routes (combined absolute average fold error (cAAFE), 1.77). The model is also found to be adequate in predicting the plasma concentration-time profiles of IDP-73152 in mice (cAAFE 1.59) and dogs (cAAFE 1.42). Assuming the oral administration of IDP-73152 to humans at doses of 640 and 1280 mg, the model is able to reproduce the concentration-time profiles obtained in humans (cAAFE 1.38); therefore, these observations indicate that the PBPK model used for IDP-73152 is applicable to animal species and humans. This model may be useful in predicting efficacious doses of IDP-73152 for the management of infectious disease in humans.