Cortisol Distribution and Metabolism in Guinea Pigs after High Doses or Treatment for Three Weeks with Indomethacin, Phenylbutazone or Chloroquine

Abstract

Guinea pigs were pretreated for three days with two daily doses intra‐peritoneally of phenylbutazone 100 mg/kg (P) or indomethacin 100 mg/kg (I ‐ 100 × 6), or for three weeks with daily single intraperitoneal injections of indomethacin 20 mg/kg (I ‐ 20 × 21) or chloroquine 35 mg/kg (C). P increased the total plasma concentration of cortisol from 441 ± 39 to 658 ± 85 ng/ml (P < 0.05) while there were no significant changes in skin cortisol (101 ± 18 to 163 ± 24 ng/g) or plasma ultrafiltrate cortisol (119 ± 12 to 179 ± 45). I ‐ 100 × 6 did not significantly change the cortisol concentrations in the plasma 630 ± 105, skin 155 ± 60 or ultrafiltrate 184 ± 62. I ‐ 20 × 21 and C caused no change in the cortisol values. The concentration of cortisol in the skin, however, is well correlated to the concentration of freely diffusible cortisol in the plasma, and for I‐100 × 6 there was a good correlation between the concentration of the drug in the plasma and the percentage of ultrafiltrable cortisol in the plasma. None of the drug treatments changed the plasma half‐life (t 1/2 ) of exogenous 4‐ 14 C‐cortisol significantly. I and C did not change the apparent volume of cortisol distribution, while P tended to increase the volume. The results do not support the theory of a displacement of cortisol from the plasma protein as a basis for the antirheumatic effect of the drugs.