Abstract
The pharmacokinetics and pharmacodynamics of intravenous furosemide, 40 mg, were studied in four normal males in a crossover fashion with and without indomethacin pretreatment. In each study 16 plasma and 10 urine samples were collected over 24 hr. Fluid and electrolyte urinary losses were replaced orally throughout the study. Unchanged furosemide and indomethacin were measured using HPLC; urinary sodium was measured by flame photometry. Pretreatment with indomethacin resulted in increased and prolonged furosemide plasma levels, increased area under the curve, decreased plasma clearance, decreased renal clearance, increased half-life, no change in volume of distribution, and decreased sodium excretion and urine volume. Analysis of sodium excretion rate with time shows that the inhibiting effect of indomethacin was greater during the first 2 hr than at later times.
Similar content being viewed by others
References
M. D. Bailie, J. A. Barbour, and J. B. Hook. Effects of indomethacin on furosemide induced changes in renal blood flow.Proc. Soc. Exp. Biol. Med. 148:1173–1176 (1975).
M. D. Bailie, K. Crosslan, and J. B. Hook. Natriuretic effect of furosemide after inhibition of prostaglandin synthetase.J. Pharmacol. Exp. Ther. 199:469–476 (1976).
J. C. Frolich, J. W. Hollifield, J. C. Dormois, B. L. Frolich, H. Seyberth, A. M. Michelakis, and J. A. Oates. Suppression of plasma renin activity by indomethacin in man.Circ. Res. 39:447–452 (1976).
M. A. Kirschenbaum, N. White, J. H. Stein, and T. A. Ferris. Redistribution of renal cortical blood flow during inhibition of prostaglandin synthesis.Am. J. Physiol. 227:801 (1974).
E. Oliw, G. Kover, C. Larsson, and E. Anggard. Reduction by indomethacin of furosemide effects in the rabbit.Eur. J. Pharmacol. 38:95–100 (1976).
R. V. Patak, B. K. Mookerjee, C. J. Bentzel, P. E. Hysert, M. Babet, and J. B. Lee. Antagonism of the effects of furosemide by indomethacin in normal and hypertensive man.Prostaglandins 10:649–659 (1975).
H. E. Williamson, W. A. Bourland, and G. R. Marchand. Inhibition of furosemide induced increase in renal blood flow by indomethacin.Proc. Soc. Exp. Biol. Med. 148:164–167 (1975).
J. L. Data, A. Rane, J. Gerkins, G. R. Wilkinson, A. S. Nies, and R. A. Branch. The influence of indomethacin on the pharmacokinetics, diuretic response and hemodynamics of furosemide in the dog.J. Pharmacol. Exp. Ther. 206:431–438 (1978).
A. Rane, O. Oelz, J. C. Frolich, H. W. Seyberth, B. J. Sweetman, J. T. Watson, G. R. Wilkinson, and J. A. Oates. Relation between plasma concentration of indomethacin and its effect on prostaglandin synthesis and platelet aggregation in man.Clin. Pharmacol. Ther. 23:658–668 (1978).
A. Greither, S. Goldman, J. S. Edelen, L. Z. Benet, and K. Cohn. Absorption of furosemide in patients with congestive heart failure.Pharmacology (in press).
W. Rupp and P. Hajdu. Pharmacokinetics and pharmacodynamics of a diuretic agent. In H. J. Dengler (ed.),Symposium on Pharmacological and Clinical Significance of Pharmacokinetics, F. K. Schattauer Verlag, Stuttgart, 1970, pp. 105–111.
W. J. Tilstone and A. Fine. Furosemide kinetics in renal failure.Clin. Pharmacol. Ther. 23:644–650 (1978).
E. T. Lin, D. E. Smith, L. Z. Benet, and B. A. Hoener. High performance liquid Chromatographic assays for furosemide in plasma and urine.J. Chromatog. (in press).
L. Z. Benet and R. L. Galeazzi. Noncompartmental determination of the volume of distribution.J. Pharm. Sci. (in press).
Author information
Authors and Affiliations
Additional information
This work was supported in part by National Institutes of Health Grants GM 16496 and AM 20884. During a portion of this work, Mr. Smith received support as a National Institutes of Health predoctoral fellow through Training Grant GM 07175.
Rights and permissions
About this article
Cite this article
Smith, D.E., Brater, D.C., Lin, E.T. et al. Attenuation of furosemide's diuretic effect by indomethacin: Pharmacokinetic evaluation. Journal of Pharmacokinetics and Biopharmaceutics 7, 265–274 (1979). https://doi.org/10.1007/BF01060017
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01060017