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Development and evaluation of physiologically based pharmacokinetic drug-disease models for predicting captopril pharmacokinetics in chronic diseases

Rasool, Muhammad F., Ali, Shazia, Khalid, Sundus, Khalid, Ramsha, Majeed, Abdul, Imran, Imran, Saeed, Hamid, Usman, Muhammad, Ali, Mohsin, Alali, Amer S., AlAsmari, Abdullah F., Ali, Nemat, Asiri, Ali Mohammed, Alasmari, Fawaz, Alqahtani, Faleh·2021·Scientific Reports
DOI 10.1038/s41598-021-88154-2
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Abstract

The advancement in the processing speeds of computing machines has facilitated the development of complex physiologically based pharmacokinetic (PBPK) models. These PBPK models can incorporate disease-specific data and could be used to predict pharmacokinetics (PK) of administered drugs in different chronic conditions. The present study aimed to develop and evaluate PBPK drug-disease models for captopril after incorporating relevant pathophysiological changes occurring in adult chronic kidney disease (CKD) and chronic heart failure (CHF) populations. The population-based PBPK simulator Simcyp was used as a modeling and simulation platform. The visual predictive checks and mean observed/predicted ratios (ratio (Obs/pred) ) of the PK parameters were used for model evaluation. The developed disease models were successful in predicting captopril PK in all three stages of CKD (mild, moderate, and severe) and CHF, as the observed and predicted PK profiles and the ratio (obs/pred) for the PK parameters were in close agreement. The developed captopril PBPK models can assist in tailoring captopril dosages in patients with different disease severity (CKD and CHF).

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Metadata

Authors
Rasool, M. F., Ali, S., Khalid, S., Khalid, R., Majeed, A., Imran, I., Saeed, H., Usman, M., Ali, M., Alali, A. S., AlAsmari, A. F., Ali, N., Asiri, A. M., Alasmari, F., & Alqahtani, F.
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2021-04-21
Volume
11
Issue
1
ISSN
2045-2322
DOI
10.1038/s41598-021-88154-2
Cited by
44
References
2
Language
en
Licence
Funders
Deanship of Scientific Research, King Saud University (RG-1441-340.)

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