European Journal of Clinical Pharmacology

, Volume 11, Issue 2, pp 149–154 | Cite as

Fluorometric determination of hydroflumethiazide in human plasma and urine after its oral administration

  • O. Brørs
  • S. Jacobsen
  • E. Arnesen
Originals

Summary

A spectrofluorometric method for determination of hydroflumethiazide in human plasma and urine has been developed. The limit of detection was 10 ng/ml plasma and 100 ng/ml urine. The plasma concentration of hydroflumethiazide was determined for 9–11 hours and excretion in urine for 24–37 hrs after oral administration of about 1 mg/kg body weight to 7 subjects. Plasma half life in healthy subjects was 1.9–2.1 h, and 2.7–8.6 h in patients during the period 4–9 hrs after dosing. Cumulative excretion in urine was 67–79% of the dose during 31–37 hrs in 6 subjects; one patient with renal disease was found to excrete only 25.8% of dose during 24 hours. Renal clearance of hydroflumethiazide was higher in the healthy subjects (0.29–0.44 1 h−1 kg−1) than in the patients (0.040–0.15 l h−1 kg−1). Plasma half life of hydroflumethiazide was not closely correlated with renal clearance of the drug, which suggests that other factors may play a role in determining plasma half life.

Key words

Hydroflumethiazide spectrofluorometry pharmacokinetics plasma half life renal excretion renal disease 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Blagg, C. R.: Hydroflumethiazide — a new oral diuretic. Lancet1959 II, 311–313Google Scholar
  2. 2.
    Dettli, L., Spring, P.: Vergleichende pharmakologische Prüfung eines neuen Salidiureticums (Cyclopenthiazid) am gesunden Menschen. Z. ges. exp. Med. exp. Chir.134, 310–322 (1960)Google Scholar
  3. 3.
    Young, D. S., Forrester, T. M., Morgan, T. N.: A comparison of the diuretic action of the chlorothiazide analogues. Lancet1959 II, 765–768Google Scholar
  4. 4.
    Matheson, N. A., Morgan, T. N.: Diuretic action of chlorothiazide. Lancet1958 I, 1195–1199Google Scholar
  5. 5.
    Ford, R. V., Moyer, J. H., Spurr, C. L.: Clinical and laboratory observations on chlorothiazide (Diuril). Arch. int. Med.100, 582–592 (1957)Google Scholar
  6. 6.
    Tapia, F. A.: Diuretic and antihypertensive effects of polythiazide. Curr. ther. Res.3, 365–377 (1961)Google Scholar
  7. 7.
    Ford, R. V.: Clinical pharmacological investigation of polythiazide, a potent oral diuretic agent. Curr. ther. Res.3, 320–329 (1961)Google Scholar
  8. 8.
    Hutcheon, D. E., Leonard, G. B.: Therapeutic efficacy of diuretics with different durations of action. J. Amer. med. Ass.185, 640–642 (1963)Google Scholar
  9. 9.
    Beevers, D. G., Harpur, J. E., Hamilton, M.: The long-term treatment of hypertension with thiazide diuretics. Postgrad. med. J.47, 639–643 (1971)Google Scholar
  10. 10.
    Maronde, R. F., Milgrom, M., Dickey, J. M.: Potassium loss with thiazide therapy. Amer. Heart. J.78, 16–21 (1969)Google Scholar
  11. 11.
    Skovbo, P., Bjerregaard, P., Hvidt, R., Jesting, E., Lorentzen, F., Hvidt, S.: Diuretika og hypokaliæmi. Ugeskr. Læg.134, 1043–1047 (1972)Google Scholar
  12. 12.
    Reutter, F., Schaub, F.: Harnsäurestoffwechsel und Salidiuretica. Dtsch. med. Wschr.89, 1101–1104 (1964)Google Scholar
  13. 13.
    Heimsoth, V., Harmann, F.: Untersuchungen zur Störung des Harnsäurestoffwechsels nach Saluretica-Verabreichung. Dtsch. med. Wschr.90, 1905–1908 (1965)Google Scholar
  14. 14.
    Roediger, P. M., Alden, J., Beardwood, D., Hutchison, J. C.: Benzothiadiazines and diabetes mellitus. II. Comparison of hyperglycemic effects of bendroflumethiazide and chlorothiazide in hypertensive patients with diabetes mellitus. Curr. ther. Res.6, 670–677 (1964)Google Scholar
  15. 15.
    Runyan, J. W.: Influence of thiazide diuretics on carbohydrate metabolism in patients with mild diabetes. New Engl. J. Med.267, 541–543 (1962)Google Scholar
  16. 16.
    Garceau, Y., Davis, J., Hasegawa, J.: Quantitative TLC procedure for determination of hydroflumethiazide in biological fluids. J. pharm. Sci.63, 1793–1795 (1974)Google Scholar
  17. 17.
    Vandenheuvel, W. J. A., Gruber, V. F., Walker, R. W., Wolf, F. J.: GLC analysis of hydrochlorothiazide in blood and plasma. J. pharm. Sci.64, 1309–1312 (1975)Google Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • O. Brørs
    • 1
    • 2
  • S. Jacobsen
    • 1
    • 2
  • E. Arnesen
    • 1
    • 2
  1. 1.Institute of PharmacologyUniversity of OsloOsloNorway
  2. 2.Medical Department VIIUllevål HospitalOsloNorway

Personalised recommendations