In-vivo Meloksikam Miktar Tayininin Validasyonu ve Tavşanlarda Meloksikam İçeren Mikropartiküller ile Biyoeşdeğerlik Çalışması

Year 2009, Issue: 2, 115 - 130, 01.06.2009

Hakan Eroğlu Nihan Burul-bozkurt Serdar Uma Levent Öner

Abstract

Meloksikam, analjezik ve antipiretik etkileri olan ve steroidal olmayan anti-inflamatuvar ilaçlar grubuna dahil bir etkin maddedir. Düşük çözünürlük ve yüksek permeabilite özellikleri ile Biyofarmasötik Sınıflandırma Sitemine gore Sınıf II grubuna dahildir. Bu çalışmada meloksikam içeren mikropartikül formülasyonlarının oral olarak tavşanlara uygulanmasından sonra miktar tayininin yapılabilmesine yönelik olarak hızlı ve basit bir HPLC yöntemi valide edilmiştir. AUC0- ∞, tmaks, t1/2, and Cmaks değerleri üzerinden farmakokinetik parametreler değerlendirilmiştir. AUC0-∞ and Cmaks değerlerinin gerekli logaritmik dönüşümleri sonrasında güven aralığı değerleri sırasıyla %68.38-147.87 ve %78.85-161.49 olarak bulunmuştur. Bu sonuçlar doğrultusunda, biyoeşdeğer olarak kabul edilme sınırları olan %80-125 aralığının dışında kalmalarından dolayı bu iki mikropartikül formülasyonlarının biyoeşdeğer olmadıkları gösterilmiştir.

Keywords

Meloksikam, Biyoeşdeğerlik, Mikropartikül

Validation of the Analytical Method for In-Vivo Determination of Meloxicam and Bioequivalence Study from Meloxicam Containing Microparticle Formulations in Rabbits

Abstract

Meloxicam is a member of non-steroidal anti-inflammatory drugs having analgesic and anti-pyretic effects. It belongs to the Biopharmaceutics Classification System Class II with its low solubility and high permeability profile. In this study, we have validated a rapid and simple HPLC method for the in-vivo determination of meloxicam from rabbit plasma after oral administration of microparticle formulations containing meloxicam. The pharmacokinetic parameters of AUC0-∞ , tmax, t1/2, and Cmax were determined for the microparticle formulations. After necessary logarithmic transformation of the AUC0-∞ and Cmax values, the confidence interval limits for both AUC0-∞ and Cmax values were calculated as 68.38-147.87% and 78.85-161.49%, respectively. These results indicated that these two microparticle formulations were not bioequivalent, since they were both out of the range for the establishment of bioequivalence which is 80-125%.

Keywords

Meloxicam, Bioequivalence, Microparticle

References

• Lewis, P.J. and C.T. Dollery: Clinical pharmacology and potential of prostacyclin, Br Med Bull, 39281-4 (1983).
• Samad, T.A., A. Sapirstein and C.J. Woolf: Prostanoids and pain: unraveling mechanisms and revealing therapeutic targets, Trends Mol Med, 8390-6 (2002).
• Garavito, R.M., M.G. Malkowski and D.L. DeWitt: The structures of prostaglandin endoperoxide H synthases-1 and -2, Prostaglandins Other Lipid Mediat, 68-69129-52 (2002).
• Smith, W.L., R.M. Garavito and D.L. DeWitt: Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2, J Biol Chem, 27133157-60 (1996).
• Davies, N.M. and N.M. Skjodt: Clinical pharmacokinetics of meloxicam. A cyclo- oxygenase-2 preferential nonsteroidal anti-inflammatory drug, Clin Pharmacokinet, 36115-26 (1999).
• Guidance for Industry: Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on Biopharmaceutical Classification System. 2000, U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research.
• Eroğlu, H., In vitro/In vivo Correlation of Class II Drugs from Controlled Release Formulations, in Department of Pharmaceutical Technology. 2007, Hacetepe University: Ankara.
• Gonzalez-Rodriguez, M.L., et al.: Alginate/chitosan particulate systems for sodium diclofenac release, Int J Pharm, 232225-34 (2002).
• Velpandian, T., et al.: Development and validation of a new high-performance liquid chromatographic estimation method of meloxicam in biological samples, J Chromatogr B Biomed Sci Appl, 738431-6 (2000).
• Niopas, I. and A.C. Daftsios: Determination of nifedipine in human plasma by solid- phase extraction and high-performance liquid chromatography: validation and application to pharmacokinetic studies, J Pharm Biomed Anal, 321213-8 (2003).
• Guidance for Industry, q2B Validation of Analytical Procedures: Methodology,. 1996, U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research
• McGilveray, I.J., Bioequivalence: A Canadian Regulatory Perspective, in Pharmaceutical Bioequivalence, J. Swarbrick, Editor. 1991, Marcel Dekker: New York. p. 381-418.
• Guidance for Industry: Bioavailability and bioequivalence studies for orally administered drug products-general considerations. 2000, U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research.
• Turner, P.V., H.C. Chen and W.M. Taylor: Pharmacokinetics of meloxicam in rabbits after single and repeat oral dosing, Comp Med, 5663-7 (2006).