Simulation of the pharmacokinetics of bisoprolol in healthy adults and patients with impaired renal function using whole-body physiologically based pharmacokinetic modeling.

AIM: To develop and evaluate a whole-body physiologically based pharmacokinetic (WB-PBPK) model of bisoprolol and to simulate its exposure and disposition in healthy adults and patients with renal function impairment. METHODS: Bisoprolol dispositions in 14 tissue compartments were described by perfusion-limited compartments. Based the tissue composition equations and drug-specific properties such as log P, permeability, and plasma protein binding published in literatures, the absorption and whole-body distribution of bisoprolol was predicted using the 'Advanced Compartmental Absorption Transit' (ACAT) model and the whole-body disposition model, respectively. Renal and hepatic clearances were simulated using empirical scaling methods followed by incorporation into the WB-PBPK model. Model refinements were conducted after a comparison of the simulated concentration-time profiles and pharmacokinetic parameters with the observed data in healthy adults following intravenous and oral administration. Finally, the WB-PBPK model coupled with a Monte Carlo simulation was employed to predict the mean and variability of bisoprolol pharmacokinetics in virtual healthy subjects and patients. RESULTS: The simulated and observed data after both intravenous and oral dosing showed good agreement for all of the dose levels in the reported normal adult population groups. The predicted pharmacokinetic parameters (AUC, C(max), and T(max)) were reasonably consistent (<1.3-fold error) with the observed values after single oral administration of doses ranging from of 5 to 20 mg using the refined WB-PBPK model. The simulated plasma profiles after multiple oral administration of bisoprolol in healthy adults and patient with renal impairment matched well with the observed profiles. CONCLUSION: The WB-PBPK model successfully predicts the intravenous and oral pharmacokinetics of bisoprolol across multiple dose levels in diverse normal adult human populations and patients with renal insufficiency.

[Bisoprolol: opportunities in the treatment of hypertension].

Bisoprolol (bisoprolol fumarate) - -cardioselective blocker, does not possess intrinsic sympathomimetic and membrane stabilizing activity. The main indications for bisoprolol are arterial hypertension (AH) and heart failure. This article provides an overview of the literature on the potential uses of bisoprolol in the treatment of hypertension. The features of the pharmacokinetics of the drug. The data on the effectiveness of bisoprolol in hypertension and tolerability in patients with concomitant disorders: diabetes, chronic obstructive pulmonary disease, peripheral atherosclerosis. Proofs of the high efficiency of antianginal bisoprola and justified the use of the drug in patients with hypertension and coronary heart disease. The capabilities of bisoprolol in the perioperative correction of hypertension. The data and pharmacoeconomic properties of bisoprolol generic counterparts.