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Arzneimittelforschung 2011; 61(12): 681-684
DOI: 10.1055/s-0031-1300587
Anticoagulants · Antithrombotics · Anti-varicosis Drugs · Blood Flow Stimulants
Editio Cantor Verlag Aulendorf (Germany)

Bioequivalence study of two clopidogrel film-coated tablet formulations in healthy volunteers

Effi Setiawati
1   PT Equilab International, Bioavailability and Bioequivalence Laboratory, Jakarta, Indonesia
,
Danang Agung Yunaidi
1   PT Equilab International, Bioavailability and Bioequivalence Laboratory, Jakarta, Indonesia
,
Lucia Rat Handayani
1   PT Equilab International, Bioavailability and Bioequivalence Laboratory, Jakarta, Indonesia
,
Iwan Dwi Santoso
1   PT Equilab International, Bioavailability and Bioequivalence Laboratory, Jakarta, Indonesia
,
Arini Setiawati
2   Department of Pharmacology and Therapeutics, Medical Faculty, University of Indonesia, Jakarta, Indonesia
,
Raymond R. Tjandrawinata
3   Dexa Laboratories of Biomolecular Sciences (DLBS), Cikarang, Indonesia
› Author Affiliations
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Publication History

Publication Date:
09 February 2012 (online)

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Abstract

The present study was performed to compare the bioavailability of two clopidogrel 75 mg film-coated tablet formulations (test formulation and reference formulation). This study was a randomized, single-blind, two-period, two-sequence cross-over study which included 24 healthy adult male and female subjects under fasting condition. The pharmacokinetic parameters were assessed based on the concentrations of clopidogrel (CAS 120202-66-6) parent compound. In each of the two study periods (separated by a washout of one week) a single dose of test or reference drug was administered.

Plasma concentrations of the drug were determined by LC-MS/MS method. The pharmacokinetic parameters assessed in this study were area under the plasma concentration-time curve from time zero to 24 h (AUCt), area under the plasma concentration-time curve from time zero to infinity (AUCinf), the peak plasma concentration of the drug (Cmax), time needed to achieve the peak plasma concentration (tmax), and the elimination half life (t1/2).

The geometric mean ratios (90% CI) of the test drug/reference drug for clopidogrel parent compound were 95.19% (81.63–110.90%) for AUCt,95.55% (80.50–113.42%) for AUCinf, and 100.18% (80.87–124.09%) for Cmax. The 90% confidence intervals calculated for AUCt and Cmax of clopidogrel parent compound were within the standard bioequivalence range (80–125% for AUC and Cmax). It was concluded that the two clopidogrel film-coated tablets (test and reference drug) were bioequivalent in terms of the rate and extent of absorption.

Key words

Adenylate cyclase-coupled ADP receptors - Bioavailability - Bioequivalence - Clopidogrel bisulphate - Clopidogrel parent compound - Pharmacokinetics
 

  • References

  • 1 Badan Pengawas Obat dan Makanan. Pedoman Uji Bioeki-valensi. [Guideline for Bioequivalence Studies.] Jakarta: BPOM; 2004.
    PubMed
  • 2 Badan Pengawas Obat dan Makanan. Pedoman Cara Uji Klinik yang Baik. [Guideline for Good Clinical Practice.] Jakarta: BPOM; 2001.
    PubMed
  • 3 Rossi S. Australian Medicines Handbook. Adelaide (SA): Australian Medicines Handbook Pty Ltd; 2005. p. 295.
    PubMed
  • 4 Lainesse A, Ozalp Y, Wong H, Alpan RS. Bioequivalence study of clopidogrel bisulfate film-coated tablets. Arzneimittelforschung. 2004; 54 (9a) 600-4
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Rxlist. Plavix: description, chemistry, ingredients, pharmacology, pharmacokinetics, studies and metabolism of clopidogrel: monograph. [Online]. 2009 [cited 20 May 2009]; Available from: www.rxlist.com/plavix-drug.htm
    PubMed
  • 6 Antic D, Filipic S, Agbaba D. A simple and sensitive TLC method for determination of clopidogrel and its impurities SR 26334 in pharmaceutical products. Acta Chromatogr. 2008; 17: 199-206
    PubMedGoogle Scholar