Summary
The interaction between isofezolac and probenecid has been studied with the aid of a specific HPLC assay for isofezolac in plasma and urine. 8 healthy adult volunteers received a single 40 mg oral dose of isofezolac before and after 3 days of loading with 0.5 g probenecid t.i.d. There was an increase in the maximum plasma isofezolac concentration from 2.44 to 3.38 µg · ml−1 when probenecid was given. The AUC of isofezolac in plasma increased from 6.73 to 11.28 µg · h · ml−1. After the last dose in a 7 day treatment with 40 mg isofezolac t.i.d., there was an increase in the maximum plasma isofezolac level from 2.84 to 4.96 µg · ml−1 when probenecid was given. The rate of absorption of isofezolac was not affected. An increase in the AUC of isofezolac in plasma was observed from 11.74 to 26.34 µg · h · ml−1. The major effect of probenecid on isofezolac metabolism was a 50% reduction in total isofezolac (free+conjugates) excreted inurine. Because of this interaction, patients given isofezolac combined with probenecid will have a higher steady-state plasma level of isofezolac than when probenecid is not administered.
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References
Baber N, Halliday L, Sibeon R, Littler T, L'E Orme M (1978) The interaction between indomethacin and probenecid. A clinical and pharmacokinetic study. Clin Pharmacol Ther 24: 298–307
Bannier A, Brazier JL (1980) Determination of isofezolac in biological fluids by reversed-phase liquid column chromatography. J Chromatogr 182: 369–377
Bannier A, Brazier JL, Soubeyrand J (1982) Dosage de l'isofezolac dans les milieux biologiques. Applications à la pharmacocinétique. 1er Congrès Européen de Biopharmacie et Pharmacocinétique, Lavoisier (ed.), Paris, pp. 201–209
Mizoule J, Lefur G, Uzan A (1979) Study of two new non-steroid anti-inflammatory drugs having a pyrazole structure (LM 22070 and LM 22102). Arch Int Pharmacodyn 238: 305–332
Runkel R, Mroszczak E, Chaplin M, Sevelius H, Segre E (1978) Naproxen-Probenecid interaction. Clin Pharmacol Ther 24: 706–713
Upton RA, Williams RL, Buskin JN, Matthew-Jones R (1982) Effects of probenecid on ketoprofen kinetics. Clin Pharmacol Ther 31: 705–712
Veenendaal JR, Brooks AM, Meffin PJ (1981) Probenecid-clofibrate interaction. Clin Pharmacol Ther 29: 351–358
Weiner IM, Washington JA, Mudge GM (1969) On the mecanism of action of probenecid on renal tubular excretion. Bull Johns Hopkins Hosp 166: 333–346
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Bannier, A., Comet, F., Soubeyrand, J. et al. Effect of probenecid on isofezolac kinetics. Eur J Clin Pharmacol 28, 433–437 (1985). https://doi.org/10.1007/BF00544363
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DOI: https://doi.org/10.1007/BF00544363