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Physiologically‐based pharmacokinetics of ziprasidone in pregnant women
Author(s) -
Biesdorf Carla,
Martins Frederico S.,
Sy Sherwin K.B.,
Diniz Andrea
Publication year - 2019
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13872
Subject(s) - physiologically based pharmacokinetic modelling , ziprasidone , pharmacokinetics , medicine , population , pregnancy , pharmacology , physiology , antipsychotic , psychiatry , biology , environmental health , schizophrenia (object oriented programming) , genetics
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, C max and t max 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, C max and t max 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.