Pharmacokinetics, Safety, and Tolerance of Anagrelide, the First Domestic Generic, Compared with Reference Drug

AUTOIMMUNE THROMBOCYTOPENIA ,

SK Zyryanov1,2, VV Chistyakov1, OI Butranova1, ES Stepanova1, OG Potanina1, RA Abramovich1

1 RUDN University, 6 Miklukho-Maklaya str., Moscow, Russian Federation, 117198

2 Municipal Clinical Hospital No. 24, 10 Pistsovaya str., Moscow, Russian Federation, 127015

For correspondence: Olga Igorevna Butranova, MD PhD, 6 Miklukho-Maklaya str., Moscow, Russian Federation, 117198; Tel.: +7(903)376-71-40; e-mail: butranova-oi@rudn.ru, butranovaolga@mail.ru

For citation: Zyryanov SK, Chistyakov VV, Butranova OI, et al. Pharmacokinetics, Safety, and Tolerance of Anagrelide, the First Domestic Generic, Compared with Reference Drug. Clinical oncohematology. 2020;13(3):346–53. (In Russ).

DOI: 10.21320/2500-2139-2020-13-3-346-353

ABSTRACT

Background. Anagrelide is used for the treatment of essential thrombocythemia. This drug selectively affects thrombocytes without inducing pronounced myelosuppression, which provides a satisfactory safety profile.

Aim. To compare pharmacokinetics and to assess bioequivalence of two anagrelide drugs for oral administration in healthy volunteers.

Materials & Methods. Open, randomized, two-period, two-sequence, crossover study comparing pharmacokinetics and bioequivalence of anagrelide included 30 volunteers. The participants received a single dose of either test or reference drug, depending on the study period. Serial blood samples for pharmacokinetic analysis were collected within 12 hours after drug administration. Plasma anagrelide concentration was measured by high-performance liquid chromatography/mass spectrometry. Pharmacokinetic parameters were analyzed by non-compartmental method. ANOVA analysis of variance was used for assessing the difference between the mean values of the AUC0-t, AUC0-∞ and Cmax pharmacokinetic parameters at 5 % significance level.

Results. The mean values of maximum concentration (Сmax) after a single dose of anagrelide were 12.68 ± 2.99 ng/mL and 12.46 ± 3.15 ng/mL for test and reference drugs, respectively. Relative bioavailability was 1.16 ± 0.18. The AUC0-12 mean values calculated by anagrelide concentrations after a single dose of test and reference drugs were 30.38 ± 7.0 ng • h/mL and 28.78 ± 7.50 ng • h/mL, respectively, and the AUC0-∞ mean values were 31.13 ± 7.15 ng • h/mL and 29.55 ± 7.61 ng • h/mL, respectively. The assessment of main vital functions and laboratory parameters did not reveal any effect of the drugs on the health status of trial participants.

Conclusion. Pharmacokinetic profile of the test drug (generic anagrelide) did not considerably differ from that of reference drug, which indicates in vivo bioequivalence of it. The assessment of drug safety yielded satisfactory tolerance; no serious adverse events have been reported.

Keywords: anagrelide, generic, bioequivalence, essential thrombocythemia, safety, tolerance.

Received: February 19, 2020

Accepted: May 25, 2020

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