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Although rifampicin (RFP) is known to be one of the potent hepatic microsomal enzyme inducers, little has been reported about the detailed pharmacokinetics of glucocorticoids in patients under RFP therapy. In this paper, the metabolism of cortisol, prednisolone and dexamethasone were investigated comparatively by simultaneous injection of these glucocorticoids. Eleven patients under RFP therapy, including 7 with tuberculosis together with collagen diseases and 4 with tuberculosis alone, were studied. Sixteen normal volunteers and 4 patients with collagen diseases not under RFP therapy were also examined as controls. After 1 mg of betamethasone was administered orally on the previous night for the suppression of endogenous cortisol, a mixed solution of 1 mg each of cortisol, prednisolone and dexamethasone was given intravenously. Plasma steroid levels of periodically collected blood samples were determined by respective radioimmunoassay after extraction with dichloromethane and purification by paper chromatography. Half-times of plasma disappearance (t 1/2), metabolic clearance rates (MCR) and total apparent distribution volumes (V) of these glucocorticoids were calculated using the single compartment model. The mean values of t 1/2 of cortisol, prednisolone and dexamethasone in patients with collagen diseases under RFP therapy were 1.8 +/- 0.3 (Mean +/- SD) (p less than 0.05), 1.4 +/- 0.2 (p less than 0.001) and 1.3 +/- 0.3 hours (p less than 0.001), respectively, which were significantly shortened when compared with normal subjects (cortisol, 2.1 +/- 0.2; prednisolone, 2.5 +/- 0.7; dexamethasone, 3.5 +/- 1.0 hours). The MCR of cortisol, prednisolone and dexamethasone in these patients were 139 +/- 57, 141 +/- 53 (p less than 0.01) and 722 +/- 137 l/day/m2 (p less than 0.001), respectively, which were increased when compared with normal subjects (cortisol, 114 +/- 20; prednisolone, 75 +/- 25; dexamethasone, 153 +/- 45 l/day/m2). The metabolism of these glucocorticoids in patients with collagen diseases under RFP therapy were also accelerated when compared with those in patients with collagen diseases not under RFP therapy. The t 1/2 of cortisol, prednisolone and dexamethasone in patients with tuberculosis alone under RFP therapy were 1.3 +/- 0.3 (p less than 0.001), 1.4 +/- 0.5 (p less than 0.01) and 1.2 +/- 0.3 hours (p less than 0.001), respectively, which were significantly shortened when compared with normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

A Comparative Study of the Accelerated Metabolism of Cortisol, Prednisolone and Dexamethasone in Patients under Rifampicin Therapy