Effect of altered urinarypH on tetracycline and doxycycline excretion in humans

  • James M. Jaffe
  • John L. Colaizzi
  • Rolland I. Poust
  • Robert H. McDonaldJr.


The effect of altered urinary pH on the excretion of single doses of orally administered tetracycline hydrochloride and doxycycline hyclate was studied in humans. Alkalinization of the urine significantly enhanced the cumulative renal excretion of both tetracycline and doxycycline as compared to acidic urine treatments. Altered tubular reabsorption was assumed to have caused this effect, since tetracyclines have been shown to be more lipid soluble at their isoelectric pH (approximately the pH of the acidic urine treatment) as compared to more alkaline pHs. The renal clearance of doxycycline was significantly increased by urinary alkalinization.

Key words

tetracycline hydrochloride doxycycline hyclate urinarypexcretion 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    M. D. Milne. Influence of acid-base balance on efficacy and toxicity of drugs.Proc. Roy. Soc. Med.58: 961–963 (1965).PubMedCentralPubMedGoogle Scholar
  2. 2.
    M. D. Milne, B. H. Schribner, and M. A. Crawford. Non-ionic diffusion and excretion of weak acids and bases.Am. J. Med. 24: 709–729 (1958).PubMedCrossRefGoogle Scholar
  3. 3.
    B. B. Brodie and C. A. M. Hogben. Some physico-chemical factors in drug action.J. Pharm. Pharmacol. 9: 345–380 (1957).PubMedCrossRefGoogle Scholar
  4. 4.
    A. H. Beckett and G. R. Wilkinson. Influence of urinepH and flow rate on the renal excretion of chlorpheniramine in man.J. Pharm. Pharmacol. 17: 256–257 (1965).PubMedCrossRefGoogle Scholar
  5. 5.
    H. B. Kostenbauder, J. P. Portnoff, and J. V. Swintosky. Control of urinepH and its effect on sulfaethidole excretion in humans.J. Pharm. Sci. 51: 1084–1089 (1962).PubMedCrossRefGoogle Scholar
  6. 6.
    A. H. Beckett and M. Rowland. Urinary excretion kinetics of methylamphetamine in man.J. Pharm. Pharmacol. 17: Suppl. 109S-114S (1965).CrossRefGoogle Scholar
  7. 7.
    H. B. Haag, P. S. Larson, and J. J. Schwartz. The effect of urinarypH on the elimination of quinine in man.J. Pharmacol. Exptl. Therap. 79: 136–139 (1943).Google Scholar
  8. 8.
    A. M. Asatoor, D. R. London, M. D. Milne, and M. L. Simenhoff. The excretion of pethidine and its derivatives.Brit. J. Pharmacol. 20: 285–298 (1963).PubMedCentralPubMedGoogle Scholar
  9. 9.
    J. L. Colaizzi and P. R. Klink.pH partition behavior of tetracyclines.J. Pharm. Sci. 58: 1184–1189 (1969).PubMedCrossRefGoogle Scholar
  10. 10.
    I. O'Reilly and E. Nelson. Urinary excretion kinetics for evaluation of drug absorption IV.J. Pharm. Sci. 50: 413–416 (1961).PubMedCrossRefGoogle Scholar
  11. 11.
    N. H. Steigbel, C. W. Reed, and M. Finland. Absorption and excretion of five tetracycline analogues in normal young men.Am. J. Med. Sci. 255: 296–312 (1968).CrossRefGoogle Scholar
  12. 12.
    J. T. Doluisio and L. W. Dittert. Influence of repetitive dosing of tetracyclines on biologic half-life in serum.Clin. Pharmacol. Therap. 10: 690–701 (1969).Google Scholar
  13. 13.
    A. Engelund, P. Terp, and C. Trolle-Larsen. Studies on renal excretion of tetracycline.Acta Pharmacol. Toxicol. 12: 227–232 (1956).CrossRefGoogle Scholar
  14. 14.
    J. Fabre, J. S. Pitton, and J. P. Kuntz. Distribution and excretion of doxycycline in man.Chemotherapia 11: 73–85 (1966).CrossRefGoogle Scholar
  15. 15.
    K. W. Kohn. Determination of tetracyclines by extraction of fluorescent complexes.Anal. Chem. 33: 862–965 (1961).CrossRefGoogle Scholar
  16. 16.
    T. Chulski, R. H. Johnson, C. A. Schlagel, and J. G. Wagner. Direct proportionality of urinary excretion rate and serum level of tetracycline in human subjects.Nature 207: 1301–1302 (1965).CrossRefGoogle Scholar
  17. 17.
    W. H. Barr, L. M. Gerbracht, K. Letcher, M. Plaut, and N. Strahl. Assessment of the biologic availability of tetracycline products in man.Clin. Pharmacol. Therap. 13: 97–108 (1972).Google Scholar
  18. 18.
    A. Edwards.Statistical Methods, 2nd ed., Holt, Rinehart, and Winston, New York (1967), pp. 215–220.Google Scholar
  19. 19.
    J. V. Swintosky. Excretion equations and interpretation for digitoxin.Nature 79: 98–99 (1957).CrossRefGoogle Scholar
  20. 20.
    B. J. Beibowitz, J. L. Hakes, M. M. Cahn, and E. J. Levy. Doxycycline blood levels in normal subjects after intravenous and oral administration.Curr. Therap. Res. 14: 820–832 (1972).Google Scholar
  21. 21.
    W. J. Youden.Statistical Methods for Chemists, Wiley, New York (1951), pp. 45–47.Google Scholar
  22. 22.
    C. M. Kunin and M. Finland. Clinical pharmacology of the tetracycline antibiotics.Clin. Pharmacol. Therap. 2: 51–69 (1961).Google Scholar
  23. 23.
    W. H. Barr, J. Adair, and L. Garrettson. Decrease of tetracycline absorption in man by sodium bicarbonate.Clin. Pharmacol. Therap. 12: 779–784 (1972).Google Scholar
  24. 24.
    W. J. Jusko and M. Gibaldi. Effects of change in elimination in various parameters of the two compartment open model.J. Pharm. Sci. 61: 1270–1273 (1972).PubMedCrossRefGoogle Scholar
  25. 25.
    C. R. Stephens, K. Murai, K. J. Brunings, and R. B. Woodward. Acidity constants of the tetracycline antibiotics.J. Am. Chem. Soc. 78: 4155–4158 (1956).CrossRefGoogle Scholar
  26. 26.
    C. R. Stephens, K. Murai, H. Rennhard, L. H. Conover, and K. J. Bruning. Hydrogenolysis Studies in the tetracycline series, 6-deoxytetracycline.J. Am. Chem. Soc. 80: 5324–5325 (1958).CrossRefGoogle Scholar
  27. 27.
    K. Diem and C. Letner (eds.).Scientific Tables, 7th ed., Ciba Geigy, Basel, Switzerland (1970), p. 662.Google Scholar
  28. 28.
    W. Klinger, P. Bayeryl, and H. Edel. Doxycycline in renal insufficiency.Progress in antimicrobial agents and chemotherapy 6: 134–141 (1966).Google Scholar

Copyright information

© Plenum Publishing Corporation 1973

Authors and Affiliations

  • James M. Jaffe
    • 1
  • John L. Colaizzi
    • 1
  • Rolland I. Poust
    • 1
  • Robert H. McDonaldJr.
    • 2
  1. 1.Department of Pharmaceutics, School of PharmacyUniversity of PittsburghPittsburgh
  2. 2.Department of Medicine, School of MedicineUniversity of PittsburghPittsburgh

Personalised recommendations