Summary
The fluorometric method of Holt & Hawkins (1965) has been modified to permit determination of 50 ng indomethacin in 0.5 ml plasma, by measuring its fluorescence in a phosphate buffer at pH 11.6 instead of sodium hydroxide. The method has also been adapted to show the presence of salicylic acid and a column chromatographic method has been devised for its removal. The protein binding of indomethacin in human plasma was calculated to be about 90% from an association constant of 0.86×103 M−1 (M=molarity). The number of binding sites on albumin is about 15. The plasma levels of indomethacin in patients receiving continuous treatment with Indocid® were between 0.5 and 3 µg/ml during the 4–5 h immediately after the last dose of 25 mg. The disappearance of indomethacin from plasma appears to consist of a fast primary phase at plasma concentrations greater than 1 µg/ml (T 1/2 about 90 min.), and a slower secondary phase.
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References
Harman, R.E., Meisinger, M.A.P., Davis, G.E., Kuehl, Jr., F.A.: The metabolites of indomethacin, a new anti-inflammatory drug. J. Pharmacol. exp. Ther.143, 215–220 (1964).
Holt, L.P.J., Hawkins, C.F.: Indomethacin: Studies of absorption and of the use of indomethacin suppositories. Brit. med. J.1965 I, 1354–1356.
Hucker, H.B., Zacchei, A.G., Cox, S.V., Brodie, D.A., Cantwell, N.H.R.: Studies on the absorption, distribution and excretion of indomethacin in various species. J. Pharmacol. exp. Ther.153, 237–249 (1966).
Kerckhoffs, H.P.M., Huizinga, T.: Vergelijkend onderzoek over de opname van geneesmiddelen na toediening langs orale, rectale en parenterale weg. I. Thiazinamium en indomethacine. Pharm. Weekblad102, 1183–1200 (1967).
Laurell, C.B.: Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal. Biochem.15, 45–52 (1966).
Perel, J.M., Gutman, A.B., Yu, T.F., Dayton, P.G.: Metabolism of probenecid in man: Renal disposition of its acylglucuronide. Clin. Res.18, 342 (1970).
Rosenthal, H.E.: A graphic method for the determination and presentation of binding parameters in a complex system. Anal. Biochem.20, 525–532 (1967).
Skeith, M.D., Simkin, P.A., Healey, L.A.: The renal excretion of indomethacin and its inhibition by probenecid. Clin. Pharmacol. Ther.9, 89–93 (1968).
Solomon, H.M., Schrogie, J.J., Williams, D.: The displacement of phenylbutazone-14C and warfarin-14C from human albumin by various drugs and fatty acids. Biochem. Pharmacol.17, 143–151 (1968).
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Hvidberg, E., Lausen, H.H. & Jansen, J.A. Indomethacin: Plasma concentrations and protein binding in man. Eur J Clin Pharmacol 4, 119–124 (1972). https://doi.org/10.1007/BF00562508
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DOI: https://doi.org/10.1007/BF00562508