Pharmacokinetic study of Maloben after single and multiple doses in healthy volunteers

Introduction. Maloben is a new drug for the treatment of liver diseases with previously unstudied pharmacokinetics in humans.

Aim. To determine the pharmacokinetic (PK) parameters of Maloben tablets (SPCPU, Russia) after single and multiple administrations in healthy volunteers as part of a phase I clinical trial.

Materials and methods. The phase I clinical trial was conducted in two stages. Stage I involved 24 volunteers divided into 3 cohorts of 8 volunteers each: cohort 1 received a single 60 mg dose of maloben, cohort 2 a single 120 mg dose, and cohort 3 a single 180 mg dose. Stage II included healthy volunteers who completed the previous stage: cohort 4 received a daily dose of 60 mg, cohort 5 a daily dose of 120 mg, and cohort 6 a daily dose of 180 mg. To determine maloben concentrations in plasma, high-performance liquid chromatography with tandem mass spectrometric detection (HPLC-MS/MS) was used. Based on plasma concentrations obtained during the analytical phase after single and multiple oral administrations, pharmacokinetic parameters of maloben were evaluated.

Results and discussion. Pharmacokinetic parameters of maloben were evaluated in 6 cohorts of 8 volunteers each. Mean C_max values were 18.09 ± 8.06, 41.36 ± 5.63, and 51.81 ± 11.05 ng/mL after single dosing in cohorts 1–3, and 37.93 ± 20.98, 70.83 ± 37.37, and 78.98 ± 37.03 ng/mL after multiple dosing in cohorts 4–6. Mean AUC_(0–t) values were 348.59 ± 200.65, 938.32 ± 344.95, and 1177.13 ± 221.81 ng · h/L after single dosing in cohorts 1–3, and 3142.22 ± 2091.08, 5714.73 ± 2482.56, and 7799.02 ± 3829.67 ng · h/L after multiple dosing in cohorts 4–6. Mean AUC_(0–∞) values were 623.05 ± 390.08, 1171.68 ± 471.89, and 1666.93 ± 596.25 ng · h/L after single dosing in cohorts 1–3, and 3228.41 ± 2141.08, 5789.32 ± 2539.34, and 8970.72 ± 5143.42 ng · h/L after multiple dosing in cohorts 4–6. Dose proportionality (linear PK) was established for PK parameters C_max, AUC_(0–t), and AUC_(0–∞) after single dosing, and for AUC_(0–t) and AUC_(0–∞) after multiple dosing.

Conclusion. For the first time, the pharmacokinetics of maloben under various dosing regimens in volunteers were investigated, as well as the assessment of changes in PK parameters.

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