Aims: Pregnancy is associated with physiological changes that alter the pharmacokinetics (PK) of drugs. The aim of this study was to predict the PK of ziprasidone in pregnant women.
Methods: A full physiologically-based pharmacokinetic (PBPK) model of ziprasidone was developed and validated for the non-pregnant population (healthy adults, paediatrics, geriatrics), and this was extended to the pregnant state to assess the change in PK profile of ziprasidone throughout pregnancy.
Results: The PBPK model successfully predicted the ziprasidone disposition in healthy adult volunteers, wherein the predicted and observed AUC, Cmax and tmax were within the fold-difference of 0.94-1.09, 0.89-1.40 and 0.80-1.08, respectively. The paediatric and geriatric population, also showed predicted AUC, Cmax and tmax within a two-fold range of the observed values. The simulated exposure in pregnant women using a p-PBPK model showed no significant difference when compared to non-pregnant women.
Conclusions: The PBPK model predicted the impact of physiological changes during pregnancy on PK and exposure of ziprasidone, suggesting that dose adjustment is not necessary in this special population.
Keywords: PBPK; pregnancy; ziprasidone.
© 2019 The British Pharmacological Society.