Download PDF
Drug Res (Stuttg) 2013; 63(01): 13-18
DOI: 10.1055/s-0032-1331181
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Pharmacokinetics and Bioequivalence Study of Two Indapamide Formulations after Single-dose Administration in Healthy Chinese Male Volunteers

G. Li
1   Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, P. R. China
2   Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, P. R. China
,
X. Zhang
1   Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, P. R. China
2   Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, P. R. China
,
Y. Tian
1   Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, P. R. China
2   Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, P. R. China
,
Z. Zhang
1   Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, P. R. China
2   Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, P. R. China
,
J. Rui
3   Nanjing Command General Hospital, Nanjing, P. R. China
,
X. Chu
3   Nanjing Command General Hospital, Nanjing, P. R. China
› Author Affiliations
Further Information

Publication History

received 08 June 2012

accepted 07 November 2012

Publication Date:
13 December 2012 (online)

Also available at
   Permissions and Reprints

Abstract

The pharmacokinetics and relative bioavailability/bioequivalence of 2 formulations of indapamide were assessed in this paper. The study was conducted in 20 healthy Chinese male volunteers according to an open, randomized, single-blind, 2-way crossover study design with a wash-out phase of 7 days. Blood samples for pharmacokinetic profiling were taken up to 84 h post-dose, and indapamide concentrations in plasma were determined by a validated liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method. Based on the plasma concentration-time data of each individual in each period, pharmacokinetic parameters, Cmax, AUC0–τ, AUC0–∞ and t1/2, were calculated by non-compartmental analysis. Pharmacokinetic parameters for test and reference formulations were analyzed statistically to assess bioequivalence of the 2 formulations. The values of Cmax, Tmax, t1/2, AUC0–τ, AUC0–∞ for test and reference formulations were 49.53±5.53 and 47.79±4.68 ng/mL, 1.9±0.6 and 2.0±0.5 h, 22.49±5.93 and 23.23±4.48 h, 859.51±160.92 and 840.90±170.62 ng · h/mL, 934.35±190.60 and 919.52±179.74 ng · h/mL, respectively. The 90% confidence intervals of the T/R-ratios of logarithmically transformed data were within the accepted range of 80–125%. It showed that the 2 formulations of indapamide were bioequivalent. Both preparations were well tolerated and no adverse reactions were found throughout the study.

Key words

indapamide - pharmacokinetics - bioequivalence - healthy volunteers - HPLC-MS - human plasma
 

  • References

  • 1 Ganado P, Ruiz E, Del Rio M et al. Growth inhibitory activity of indapamide on vascular smooth muscle cells. Eur J Pharmacol 2001; 428: 19-27
    CrossrefPubMedGoogle Scholar
  • 2 Campbell DB, Taylor AR, Moore RA. Observations on the pharmacokinetics of indapamide in man. Br J Clin Pharmacol 1976; 3: 971
    PubMedGoogle Scholar
  • 3 Chillon JM, Baumbach GL. Effects of indapamide, a thiazide-like diuretic, on structure of cerebral. Hypertension 2004; 43: 1092-1097
    CrossrefPubMedGoogle Scholar
  • 4 Inaba M, Noguchi Y, Yamamoto T et al. Effects of a low dose of indapamide, a diuretic, given daily or every-other-day on blood pressure and metabolic parameters. Hypertens Res 2004; 27: 141-145
    CrossrefPubMedGoogle Scholar
  • 5 Kyncl J, Oheim K, Seki T et al. Antihypertensive action of indapamide. Comparative studies in several experimental models. Arzneimittelforschung Oct 1975; 25 (10) 1491-1495
    PubMedGoogle Scholar
  • 6 Ames RP. A comparison of blood lipid and blood pressure responses during the treatment of systemic hypertension with indapamide and with thiazides. Am J Cardiol 1996; 77: 12B-l6B
    CrossrefPubMedGoogle Scholar
  • 7 Carey PA, Sheridan DJ, Cordoue A et al. Effect of indapamide on left ventricular hypertrophy in hypertension. Am J Cardiol 1996; 77: 17B-19B
    CrossrefPubMedGoogle Scholar
  • 8 Ren C, Fang L, Ling L et al. Design and in vivo evaluation of an indapamide transdermal patch. International Journal of Pharmaceutics 2009; 370: 129-135
    CrossrefPubMedGoogle Scholar
  • 9 Hang TJ, Zhao W, Liu J et al. A selective HPLC method for the determination of indapamide in human whole blood: Application to a bioequivalence study in Chinese volunteers. Journal of Pharmaceutical and Biomedical Analysis 2006; 40: 202-205
    CrossrefPubMedGoogle Scholar
  • 10 Livingstone K, McKay G, Fisher M. Indapamide. Pract Diab Int Sep 2008; 25 (07) 290-291
    CrossrefPubMedGoogle Scholar
  • 11 Caruso FS, Szabadi RR, Vukovich RA. Pharmacokinetics and clinical pharmacology of indapamide. Am heart J. 1983; Jul; 106 (1 Pt 2) 212-220
    PubMedGoogle Scholar
  • 12 Ding L, Yang L, Liu F et al. A sensitive LC–ESI-MS method for the determination of indapamide in human plasma: Method and clinical applications. Journal of Pharmaceutical and Biomedical Analysis 2006; 42: 213-217
    CrossrefPubMedGoogle Scholar
  • 13 Chen WD, Liang Y, Zhang H et al. Simple, sensitive and rapid LC–MS method for the quantitation of indapamide in human plasma—application to pharmacokinetic studies. J Chromatogr B 2006; 842: 58-63
    CrossrefPubMedGoogle Scholar
  • 14 US Department of Health and Human Services . Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Guidance for Industry. Bioanalytical Method Validation. 2001
    PubMedGoogle Scholar
  • 15 Schiavi P, Jochemsen R, Guez D. Pharmacokinetics of sustained and immediate release formulations of indapamide after single and repeated oral administration in healthy volunteers. Fundamental & Clinical Pharmacology 2000; 14: 139-146
    PubMedGoogle Scholar
  • 16 Florin A, Cristina G, Victor D et al. Liquid chromatography–electrospray tandem mass spectrometry method for determination of indapamide in serum for single/multiple dose bioequivalence studies of sustained release formulations. J Chromatogr B 2005; 816: 35-40
    CrossrefPubMedGoogle Scholar
  • 17 Campbell DB, Taylor AR, Hopkins YW et al. Pharmacokinetics and metabolism of indapamide: A review. Current Medical Research and Opinion 1977; 5 (Suppl. 01) 13-24
    CrossrefPubMedGoogle Scholar
  • 18 Zendelovska D, Stafilov T, Stefova M. Optimization of a solid-phase extraction method for determination of indapamide in biological fluids using high-performance liquid chromatography. J Chromatogr B 2003; 788: 199-206
    CrossrefPubMedGoogle Scholar
  • 19 Jain DS, Subbaiah G, Sanyal M et al. Liquid chromatography–tandem mass spectrometry validated method for the estimation of indapamide in human whole blood. J Chromatogr B 2006; 834: 149-154
    CrossrefPubMedGoogle Scholar