Apparent dose-dependent absorption of chlorothiazide in dogs

  • Dennis E. Resetarits
  • Theodore R. Bates
Article

Abstract

The purpose of this study was to determine the effect of oral dose on the absorption of chlorothiazide in the dog. Chlorothiazide was quantitatively excreted in the urine after administration of 50-mg and 250-mg intravenous doses. In contrast, the urinary recovery of chlorothiazide after oral administration showed appreciable interanimal variation and decreased from 70.4% to 26.7% on the average as the oral dose was increased from 125 mg to 750 mg. Oral administration of a single 15-mg dose of propantheline bromide (a potent inhibitor of gastric emptying and intestinal motility) at −1 hr increased the absorption of a 250 mg oral dose of chlorothiazide in three out of four dogs. These results suggest that chlorothiazide absorption is dose dependent and apparently site specific.

Key words

absorption dose-dependent absorption chlorothiazide urinary excretion dogs 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    E. A. Swinyard.Diuretic Drugs. InRemington's Pharmaceutical Sciences, Chap. 49, Mack Publishing Co., Easton, Pa., 1975, p. 896.Google Scholar
  2. 2.
    J. E. Baer, H. L. Leedy, A. V. Brooks, and K. H. Beyer. The physiological disposition of chlorothiazide (Diuril) in the dog.J. Pharmacol. Exp. Ther. 125:295–302 (1959).PubMedGoogle Scholar
  3. 3.
    K. H. Beyer. The mechanism of action of chlorothiazide.Ann. N.Y. Acad. Sci. 71:363–379 (1958).PubMedCrossRefGoogle Scholar
  4. 4.
    H. R. Brettell, J. K. Aikawa, and G. S. Gordon. Studies with chlorothiazide tagged with radioactive carbon (C14) in human beings.Arch. Intern. Med. 106:57–63 (1960).PubMedCrossRefGoogle Scholar
  5. 5.
    M. C. Meyer and A. B. Straughn. Factors affecting the bioavailability of chlorothiazide in man.Curr. Ther. Res. 22:573–582 (1977).Google Scholar
  6. 6.
    E. T. Lin and L. Z. Benet. High pressure liquid chromatographic determination of chlorothiazide (CT) and hydrochlorothiazide (HCT) in human serum and urine.APhA Acad. Pharm. Sci. 8(1): 194 (1978).Google Scholar
  7. 7.
    R. E. Kauffman and D. L. Azarnoff. Effect of colestipol on gastrointestinal absorption of chlorothiazide in man.Clin. Pharmacol. Ther. 14:886–890 (1973).PubMedGoogle Scholar
  8. 8.
    M. C. Meyer.Personal communication. College of Pharmacy, University of Tennessee Center for Health Sciences, Memphis, Tenn., 1978.Google Scholar
  9. 9.
    H. Sheppard, T. F. Mowles, and A. J. Plummer. Determination of hydrochlorothiazide in urine.J. Pharm. Sci. 49:722–723 (1960).CrossRefGoogle Scholar
  10. 10.
    V. P. Shah, P. Sojka, V. K. Prasad, and B. E. Cabana. Thiazide II. HPLC analysis of chlorothiazide in plasma and urine following oral administration to normal subjects.Curr. Ther. Res. 24:366–377 (1978).Google Scholar
  11. 11.
    J. P. Hunt, V. P. Shah, V. K. Prasad, and B. E. Cabana. Thiazide. I. Limitations of Bratton-Marshall colorimetric assay method and its modifications in the determination of chlorothiazide in bioequivalency studies.APhA Acad. Pharm. Sci. 8(1):195 (1978).Google Scholar
  12. 12.
    D. E. Resetarits and T. R. Bates. Errors in chlorothiazide bioavailability estimates based on a Bratton-Marshall colorimetric method for chlorothiazide in urine.J. Pharm. Sci. 68:126–127 (1979).PubMedCrossRefGoogle Scholar
  13. 13.
    G. W. Snedecor and W. G. Cochran.Statistical Methods, 6th ed., Iowa State University Press, Ames, Ia., 1967, pp. 91–119.Google Scholar
  14. 14.
    B. Beermann, M. Groschinsky-Grind, and A. Rosen. Absorption, metabolism and excretion of hydrochlorothiazide.Clin. Pharmacol. Ther. 19:531–537 (1976).PubMedGoogle Scholar
  15. 15.
    B. Beermann and M. Groschinsky-Grind. Pharmacokinetics of hydrochlorothiazide in man.Eur. J. Clin. Pharmacol. 12:297–303 (1977).PubMedCrossRefGoogle Scholar
  16. 16.
    B. Beermann, M. Groschinsky-Grind, and B. Lindstrom. Bioavailability of two hydrochlorothiazide preparations.Eur. J. Clin. Pharmacol. 11:203–205 (1977).PubMedCrossRefGoogle Scholar
  17. 17.
    B. Beermann and M. Groschinsky-Grind. Enhancement of the gastrointestinal absorption of hydrochlorothiazide by propantheline.Eur. J. Clin. Pharmacol. 13:385–387 (1978).PubMedCrossRefGoogle Scholar
  18. 18.
    B. Beermann and M. Groschinsky-Grind. Gastrointestinal absorption of hydrochlorothiazide enhanced by concomitant intake of food.Eur. J. Clin. Pharmacol. 13:125–128 (1978).PubMedCrossRefGoogle Scholar
  19. 19.
    W. G. Crouthamel, C. R. Abolin, J. Hsieh, and J. K. Lim. IntestinalpH as a factor in selection of animal models for bioavailability testing.J. Pharm. Sci. 64:1726–1727 (1975).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1979

Authors and Affiliations

  • Dennis E. Resetarits
    • 1
  • Theodore R. Bates
    • 1
  1. 1.Department of Pharmaceutics, School of PharmacyState University of New York at BuffaloAmherst

Personalised recommendations