Pharmaceutics, Free Full-Text
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Labetalol is a drug that exhibits both alpha and beta-adrenergic receptor-blocking properties. The American Heart Association/American Stroke Association (AHA/ASA) has recommended labetalol as an initial treatment option for the management of severe hypertension. The physiologically based pharmacokinetic (PBPK) model is an in silico approach to determining the pharmacokinetics (PK) of a drug by incorporating blood flow and tissue composition of the organs. This study was conducted to evaluate the primary reasons for the difference in PK after intravenous (IV) and oral administration in healthy and diseased (renal and hepatic) populations. A comprehensive literature search was done using two databases, PubMed and Google Scholar. Various PK parameters were screened for the development of the PBPK model utilizing a population-based PK-Sim simulator. Simulations were performed after creating building blocks firstly in healthy individuals and then in diseased patients after IV and oral administration. The disposition of labetalol after IV and oral administration occurring in patients with the hepatic and renal disease was predicted. The model was evaluated by calculating the Robs/pred ratio and average fold error (AFE), which was in the two-fold error range. Moreover, Box-whisker plots were made to compare the overall concentration of the drug in the body at various stages of disease severity. The presented model provides useful quantitative estimates of drug dosing in patients fighting against severe chronic diseases.
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Pharmaceutics, Free Full-Text
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