Abstract
To identify determinants of the pharmacokinetic parameters for a total of 62 heart failure drugs and their active metabolites available in Japanese healthcare settings, data on the following pharmacokinetic parameters were collected from healthy adults: bioavailability (F), urinary excretion rate of unchanged drug (Ae), volume of distribution (Vd(p)), total body clearance (CLtot(p)), fraction unbound in plasma/serum (fuP), and blood-to-plasma drug concentration ratio (B/P). Complete data on F, Ae, Vd(p), CLtot(p), and fuP were available for 26 of the 62 drugs; however, data from official/semi-official sources in Japan were available for only 14 of the 26 drugs. To identify the determinants of clearance and volume of distribution, the clearance and volume of distribution values calculated from the whole blood drug concentrations are fundamental. The B/P required for the estimation was measured or estimated for 19 drugs. Both the determinants of clearance and volume of distribution were identified for 15 drugs. There were 26 binding-sensitive (S) drugs (fuP < 0.2) and 21 binding-insensitive (IS) drugs (fuP > 0.2). Of the S drugs, unbound drug concentrations or fuP values had been measured in pharmacokinetic studies conducted in patients with organ dysfunction for only 3 drugs (dapagliflozin, vericiguat, and tolvaptan). As for the IS drugs, pharmacokinetic studies in patients with organ dysfunction had been conducted for only 4 drugs. We found some problems in the “Precautions for use” section. One of these problems is a lack of information based on the specific results of pharmacokinetic studies for drugs for which dosing regimen adjustments are described from the viewpoint of pharmacokinetics.
https://ror.org/00wm7p047 
