Comparative pharmacokinetics of pembrolizumab after single intravenous administration to Macaca fascicularis

Background. Pembrolizumab belongs to a fundamentally new class of antitumor agents with biological source – monoclonal antibodies. when creating generic biological medicinal products, it is necessary to assess the comparability of the pharmacokinetics of the developed drug and the original (reference) drug product in relevant animal species.

Aim. To compare the pharmacokinetics of two drugs with INN pembrolizumab, concentrate for solution for infusion, administered once intravenously to Macaca fascicularis.

Materials and methods. Biosimilar RPH-075 (INN pembrolizumab, JSC R-Pharm, Russia) and reference drug Keytruda® (INN pembrolizumab, MSD International GmbH) were administered once intravenously to male monkeys (2 groups of 4 males each) at a dose of 30 mg/kg. Macaque blood samples were collected for analysis before administration and at 1, 2, 4, 8, 24, 48, 72, 144, 312, 480, 648, 984, 1320 h after administration. Plasma concentrations of the active ingredient were determined by bridging ELISA using commercially available antibodies, followed by calculation of the main pharmacokinetic parameters (Cmax, AUC, MRT, Vss, T1/2, Cl).

Results. Using antibodies more available than commercial reagent kits, the pembrolizumab assay method recommended by the antibody manufacturer has been replicated. The method has been validated and applied to the analysis of biosamples obtained in the preclinical study. There was no effect of the test drug and the reference drug upon single intravenous administration to monkeys condition and animals body weigh; drugs were found to have comparable pharmacokinetic profiles.

Conclusion. The creation of a biosimilar drug in the Russian Federation will improve the treatment of patients with cancer, reduce the cost of treatment and increase the number of patients receiving high-quality medical care.

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