Abstract
The pharmacokinetics and pharmacodynamics of intravenous bumetanide (0.250 mg/kg), alone (treatment I) and after probenecid pretreatment (treatment II), were studied in four mongrel dogs. Lactated Ringer's solution was administered by vein throughout both treatments at a flow rate of 2 ml/min to avoid fluid and electrolyte depletion. Bumetanide and probenecid concentrations were analyzed by HPLC, sodium by flame photometry, and creatinine by colorimetry. Although the probenecid markedly reduced the plasma and renal clearances of bumetanide, as well as the fraction excreted unchanged in the urine, there was no significant difference between treatments I and II in the 4-hr natriuretic and diuretic responses. However, analysis of the dose-response curves between treatments I and II showed that sodium, excretion was better correlated with bumetanide urinary excretion rate than with plasma concentration. The reasons for a poor correlation between treatments during the early time periods are discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
H. H. Frey. Pharmacology of bumetanide.Postgrad. Med. J. Suppl. 51:14–18 (1975).
U. B. Olsen. The pharmacology of bumetanide: a review.Acta Pharmacol. Toxicol. Suppl III:3–29 (1977).
M. Cohen. Pharmacology of bumetanide.J. Clin. Pharmacol. 21:537–542 (1981).
E. Bourke, M. J. A. Asbury, S. O'Sullivan, and P. B. B. Gatenby. The sites of action of bumetanide in man.Eur. J. Pharmacol. 23:283–289 (1973).
S. Jayakumar and J. B. Puschett. Study of the sites and mechanisms of action of bumetanide in man.J. Pharmacol. Exp. Ther. 201:251–258 (1977).
M. Imai. Effect of bumetanide and furosemide on the thick ascending limb of Henle's loop of rabbits and rats perfused in vitro.Eur. J. Pharmacol. 41: 409–416 (1977).
S. G. Karlander, R. Henning, and O. Lundvall. Renal effects of bumetanide, a new saluretic agent.Eur. J. Clin. Pharmacol. 6:220–223 (1973).
E. H. Østergaard, M. P. Magnussen, C. K. Nielsen, E. Eilertsen, and H. H. Frey. Pharmacological properties of 3-n-butylamino-4-phenoxy-5-sulfamylbenzoic acid (bumetanide), a new potent diuretic.Arzneim.-Forsch. 22:66–72 (1972).
M. R. Cohen, E. Hinsch, R. Vergona, J. Ryan, S. J. Kolis, and M. A. Schwartz. A comparative diuretic and tissue distribution study of bumetanide and furosemide in the dog.J. Pharmacol. Exp. Ther. 197:697–702 (1976).
P. A. Friedman and F. Roch-Ramel. Hemodynamic and natriuretic effects of bumetanide and furosemide in the cat.J. Pharmacol. Exp. Ther. 203:82–91 (1977).
S. D. Holland and H. E. Williamson. Probenecid inhibition of bumetanide-induced natriuresis in the dog.Proc. Soc. Exp. Biol. Med. 161:299–302 (1979).
A. F. Lant. Effects of bumetanide on cation and anion transport.Postgrad. Med. J. Suppl. 51:35–42 (1975).
D. C. Brater and P. Chennavasin. Effect of probenecid on response to bumetanide in man.J. Clin. Pharmacol. 21:311–315 (1981).
D. E. Smith. High-performance liquid Chromatographic assay for bumetanide in plasma and urine.J. Pharm. Sci. 71:520–523 (1982).
J. G. Wagner. Pharmacokinetic parameters estimated from intravenous data by uniform methods and some of their uses.J. Pharmacokin. Biopharm. 5:161–182 (1977).
K. Yamaoka, T. Nakagawa, and T. Uno. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations.J. Pharmacokin. Biopharm. 6:165–175 (1978).
J. G. Wagner.Fundamentals of Clinical Pharmacokinetics. Drug Intelligence Publications, Hamilton, Ill., 1975, pp. 38, 83, 349.
L. Z. Benet. Pharmacokinetics/pharmacodynamics of furosemide in man: a reviewJ. Pharmacokin. Biopharm. 7:1–27 (1979).
P. Chennavasin, R. Seiwell, D. C. Brater, and W. M. M. Liang. Pharmacodynamic analysis of the furosemide-probenecid interaction in man.Kidney Int. 16:187–195 (1979).
D. E. Smith and L. Z. Benet. Relationship between urinary excretion rate, steady-state plasma levels and diuretic response of furosemide in the rat.Pharmacology 19:301–306 (1979).
D. E. Smith, W. L. Gee, D. C. Brater, E. T. Lin, and L. Z. Benet. Preliminary evaluation of furosemide-probenecid interaction in humans.J. Pharm. Sci. 69:571–575 (1980).
T. P. Green and B. L. Mirkin. Resistance of proteinuric rats to furosemide: urinary drug protein binding as determinant of drug effect.Life Sci. 26:623–630 (1980).
N. H. G. Holford and L. B. Sheiner. Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models.Clin. Pharmacokin. 6:429–453 (1981).
T. P. Green and B. L. Mirkin. Furosemide disposition in normal and proteinuric rats: urinary drug-protein binding as a determinant of drug excretion.J. Pharmacol. Exp. Ther. 218:122–127 (1981).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Smith, D.E., Lau, H.S.H. Determinants of bumetanide response in the dog: Effect of probenecid. Journal of Pharmacokinetics and Biopharmaceutics 11, 31–46 (1983). https://doi.org/10.1007/BF01061766
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01061766