Bioequivalence study of two mirtazapine oral tablet formulations in healthy Chinese male volunteers

Int J Clin Pharmacol Ther. 2012 May;50(5):368-74. doi: 10.5414/cp201609.

Abstract

Objective: Mirtazapine is a tetracyclic antidepressant which works relating to noradrenergic and elective serotoninergic receptors. The aim of this study was to assess the pharmacokinetic properties and bioequivalence of a newly developed tablet formulation of mirtazapine with those of an established branded formulation in healthy Chinese male volunteers.

Materials and methods: A randomized, open-label, single-dose, 2-way crossover study was conducted in healthy Chinese volunteers under fasting conditions with a washout of 14 days between the study periods. A sensitive and credible high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed and validated to determine mirtazapine in human plasma.

Results: The main PK parameters of the mirtazapine test and reference tables were as follows: mean (SD) C(max), 58.715 (23.89) and 58.255 (22.34) ng/ml; AUC(0-t), 591.406 (186.79) and 596.339 (201.25) ng × h/ml; AUC(0-∞), 627.03 (201.39) and 631.521 (227.32) ng × h/ml; t(1/2), 18.941 (4.79) and 18.285 (3.91) h; t(max) 1.417 (0.61) and 1.424 (0.75) h. The 90% CI for logtransformed ratios of C(max) (88.8 - 112.4%), AUC(0-t) (93.9 - 104.9%) and AUC(0-∞) (94.5 - 105.3%) for the test and reference formulations respectively, meeting the predetermined criteria for bioequivalence.

Conclusions: Both treatments exhibited similar tolerability and safety. The test product is therefore bioequivalent to the reference product with respect to the rate and extent of mirtazapine pharmacokinetics.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / chemistry
  • Antidepressive Agents, Tricyclic / pharmacokinetics*
  • Chemistry, Pharmaceutical
  • Cross-Over Studies
  • Humans
  • Male
  • Mianserin / adverse effects
  • Mianserin / analogs & derivatives*
  • Mianserin / chemistry
  • Mianserin / pharmacokinetics
  • Mirtazapine
  • Tablets
  • Therapeutic Equivalency
  • Young Adult

Substances

  • Antidepressive Agents, Tricyclic
  • Tablets
  • Mianserin
  • Mirtazapine