Pharmacokinetic parameters, safety and drug-drug interactions of mirtazapine and tizanidine, combined in the new original drug Dorsumio®

Objective: to study the pharmacokinetic parameters and safety of Dorsumio ® (mirtazapine + tizanidine, extended-release tablets, 15 mg 6 mg, JSC Valenta Pharm, Russia) taken once by healthy volunteers in comparison with Calixta , a monocomponent drug (INN: Mirtazapine, filmcoated 30 Belupo, Drugs Cosmetics d.d., Republic Croatia) Sirdalud MR Tizanidine, modified-release capsules, Novartis Pharma AG, Switzerland) an evaluation their interactions when concomitantly or separately. Material methods. A two-stage, randomized, comparative cross-over pharmacokinetics complex was conducted. In first stage, alternated between taking one two tablets administration periods; second subjects reference monodrugs alone joint combination three periods. total 38 were randomized into study, which 14 participated 24 stage study. Quantitative levels mirtazapine tizanidine determined high-performance liquid chromatography tandem mass spectrometry. Based on data obtained, main reflecting bioavailability each calculated, mutual influence also studied. During vital signs laboratory monitored, occurrence adverse events (AEs) serious AEs recorded. Results. two-fold increase dose resulted comparable individual drugs. There no significant reciprocal effect parameters. participating mild side effects registered after use that did not require medical intervention resolved own without health consequences. Conclusion. differences profile combined form free fixed combination. It shown investigated had components.