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Arzneimittelforschung 2012; 62(11): 508-512
DOI: 10.1055/s-0032-1323659
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Pharmacokinetics and Bioequivalence of 2 Tablet Formulations of Olanzapine in Healthy Chinese Volunteers: a Randomized, Open-Label, Single-Dose Study

Q. Chen
1   Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China
,
M.-q. Zhang
1   Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China
,
Y. Liu
1   Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China
,
Y.-m. Liu
1   Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China
,
S.-j. Li
1   Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China
,
C. Lu
1   Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China
,
G.-y. Liu
1   Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China
,
Y.-l. Qi
2   Department of Chemistry, University of Warwick, Coventry, United Kingdom
,
C. Yu
1   Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China
,
J.-y. Jia
1   Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China
› Author Affiliations
Further Information

Publication History

received 29 June 2012

accepted 23 July 2012

Publication Date:
29 August 2012 (online)

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Abstract

Background:

Olanzapine is a widely used agent for the treatment of schizophrenia.

Objective:

The aim of this study was to evaluate bioequivalence of two 10-mg tablet formulations of olanzapine following single oral dose in adult male volunteers.

Methods:

This was a randomized, single-dose, open-label, crossover bioequivalence study. Plasma samples were collected before dosing and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0, 72.0, 96.0, 120.0 and 144.0 h after dosing. Plasma concentrations of olanzapine were determined by using a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. Statistical analysis of the pharmacokinetic parameters Cmax, AUC0–144, and AUC0–∞ was conducted to determine bioequivalence. Adverse events were monitored, recorded and evaluated by investigators throughout the study.

Results:

24 healthy male Chinese volunteers between the ages of 18–40 years with a body mass index (BMI) between 19 and 24 kg/m2 were enrolled in the study. The mean (SD) Cmax, AUC0–144, and AUC0–∞ values after administration of the test and reference formulations, respectively, were as follows: 18.91 (5.320) vs. 18.44 (4.758) ng/mL, 582.9 (118.23) vs. 587.3 (127.12) ng/mL · h, and 615.4 (131.39) vs. 615.8 (137.45) ng/mL · h. The 90% CIs for the ratios of AUC0–144 and Cmax were 96.9% to 102.4% and 93.7% to 110.2%, respectively. The relative bioavailability of the test formulation to reference formulation was 100.1%. Both formulations were generally well tolerated and no serious AEs were reported in the study.

Conclusions:

The 90% CIs for the ratios of mean Cmax, AUC0–144, and AUC0–∞ met the regulatory criteria for bioequivalence.

Key words

olanzapine - bioequivalence - pharmacokinetics - LC-MS/MS - adverse events
 

  • References

  • 1 FDA. Electronic Orange Book. April 2007
    PubMedSearch in Google Scholar
  • 2 Beasley Jr CM, Tollefson G, Tran P et al. Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology 1996; 14: 111-123
    CrossrefPubMedSearch in Google Scholar
  • 3 McCormack PL, Wiseman LR. Olanzapine: A review of its use in the management of bipolar I disorder. Drugs 2004; 64: 2709-2726
    CrossrefPubMedSearch in Google Scholar
  • 4 Lieberman JA, Tollefson G, Tohen M et al. HGDH Study Group. Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: A randomized, double-blind trial of olanzapine versus haloperidol. Am J Psychiatry 2003; 160 (08) 1396-1404
    CrossrefPubMedSearch in Google Scholar
  • 5 Eishafeey AH, Eisherbiny MA, Fathallah MM. A Single-Dose Randomized, Two-Way Crossover Study Comparing Two Olanzapine Tablet Products in Healthy Adult Male Volunteers Under Fasting Conditions. Clinical Therapeutics 2009; 31 (03) 600-608
    CrossrefPubMedSearch in Google Scholar
  • 6 Mitchell M, Riesenberg R, Bari MA et al. A Double-Blind, Randomized Trial to Evaluate the Pharmacokinetics and Tolerability of 30 or 40 mg/d Oral Olanzapine Relative to 20 mg/d Oral Olanzapine in Stable Psychiatric Subjects. Clinical Therapeutics 2006; 28 (06) 881-892
    CrossrefPubMedSearch in Google Scholar
  • 7 Zoccali R, Muscatello MR, Torre DL et al. Lack of a pharmacokinetic interaction between mirtazapine and the newer antipsychotics clozapine, risperidone and olanzapine in patients with chronic schizophrenia. Pharmacol Res 2003; 48 (04) 411-414
    CrossrefPubMedSearch in Google Scholar
  • 8 Callaghan JT, Bergstrom RF, Ptak LR et al. Olanzapine. Pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet 1999; 37: 177-193
    CrossrefPubMedSearch in Google Scholar
  • 9 Wu TH, Chiu CC, Shen WW et al. Phamacokinetics of olanzapine in Chinese male schizophrenic patients with various smoking behaviors. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32 (08) 1889-1893
    CrossrefPubMedSearch in Google Scholar
  • 10 World Medical Association Declaration of Helsinki (WMA). Ethical Principles for Medical Research Involving Human Subjects. Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the 52nd WMA General Assembly, Edinburgh, Scotland, October 7, 2000 http://www.wma.net/e/policy/b3.htm Accessed September 20, 2007
    PubMed
  • 11 European Agency for the Evaluation of Medicinal Products (EMEA), International Conference on Harmonisation–World Health Organization . Guideline for Good Clinical Practice. ICH topic E 6 (R1). Geneva, Switzerland: WHO; 2002. http://www.emea.europa.eu/pdfs/human/ich/013595en.pdf Accessed September 26, 2007
    Search in Google Scholar
  • 12 State Food and Drug Administration of China. Guideline for Good Clinical Principles. http://www.sda.gov.cn/WS01/CL0053/24473.html Accessed August 6, 2003
    PubMed
  • 13 Zhang MQ, Jia JY, Lu C et al. Development and validation of a liquid chromatography-isotope dilution tandem mass spectrometry for determination of olanzapine in human plasma and its application to bioavailability study. Acta Pharmaceutica Sinica 2010; 45 (06) 767-771
    PubMedSearch in Google Scholar
  • 14 Chin C, Zhang ZP, Karnes HT. A study of matrix effects on an LC/MS/MS assay for olanzapine and desmethyl olanzapine. Journal of Pharmaceutical and Biomedical Analysis 2004; 35 (05) 1149-1167
    CrossrefPubMedSearch in Google Scholar
  • 15 Berna M, Ackermann B, Ruterbories K et al. Determination of olanzapine in human blood by liquid chromatography–tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2002; 767 (01) 163-168
    PubMedSearch in Google Scholar
  • 16 Center for Drug Evaluation, State Food and Drug Administration of China. Guidance for bioavailability and bioequvlence studies of chemical drug. http://www.cde.org.cn/zdyz.do?method=largePage&id=2066 Accessed March, 2005
    PubMed
  • 17 Shumaker RC. PKCALC: A BASIC interactive computer program for statistical and pharmacokinetic analysis of data. Drug Metab Rev 1986; 17 (3–4) 331-348
    CrossrefPubMedSearch in Google Scholar
  • 18 Choi S, DiSilvio B, Unangst J et al. Effect of chronic infusion of olanzapine and clozapine on food intake and body weight gain in male and female rats. Life Sciences 2007; 81 (12) 1024-1030
    CrossrefPubMedSearch in Google Scholar