6-beta-hydroxycortisol and Tuberculosis

Treatment of tuberculosis with rifampicin in patients with pre-existing adrenal failure has been reported to induce adrenal crisis due to alteration of cortisol metabolism by induction of hepatic mixed liver oxygenase enzymes. To determine whether mineralocorticoid metabolism is altered by rifampicin treatment, we established the pharmacokinetics of immunoreactive aldosterone. The metabolic clearance rate (MCR) and plasma half-life of this material were measured before and after 6 days of rifampicin treatment (600 mg/day) in seven patients with Addison's disease due to tuberculosis. Antipyrine clearance and urinary 6-beta-hydroxycortisol excretion was determined to demonstrate induction of the cytochrome P450 dependent enzymes. Infusion of aldosterone at a constant rate of 0.17 mg/h over 4.5 h produced steady state concentrations after 2 h, with no difference before and after rifampicin treatment (mean +/- SD, 1649 +/- 144 vs 1586 +/- 80 pg/ml, respectively). The disappearance curve of IR-aldosterone from plasma was biexponential. No change could be observed in the plasma half-lives (alpha-phase 29 +/- 1.9 min vs 30 +/- 1.5 min, beta-phase 129 +/- 3.2 min vs 126 +/- 4.3 min), the MCR (1.47 +/- 0.1 l/h/kg vs 1.46 +/- 0.1 l/h/kg), and the volume of distribution (9.9 +/- 1.9 vs 10.2 +/- 0.3 l). The antipyrine half-life decreased significantly from 12.2 +/- 2.6 h to 7.6 +/- 0.9 h (P less than 0.05) with a rise in antipyrine clearance from 0.38 +/- 0.07 to 0.80 +/- 0.23 ml/min/kg (P less than 0.05) and no change in the volume of distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Addison Disease; Adult; Aldosterone; Antipyrine; Female; Humans; Hydrocortisone; Male; Middle Aged; Rifampin; Tuberculosis

To determine the effect of rifampicin therapy on hepatic oxidase activity in animal protein deficient patients antipyrine and quinine t 1/2 and 6B-hydroxycortisol (6B-OHF) excretion was studied in 8 Indian vegetarians during treatment for tuberculosis. In 4 patients at the start of treatment rifampicin/streptomycin caused a steady decline in by time antipyrine t 1/2 which was complete in 3 weeks, in one patient introduction of isoniazid produced a temporary reversal. After 4 months rifampicin/isoniazid 6B-OHF excretion was increased 2 to 10 fold in all patients although one followed serially showed a marked fall when isoniazid was begun. Decline in antipyrine t 1/2 persisted in 4 patients at the end of 18 months therapy and in one of these concurrent quinine t 1/2 confirmed partial isoniazid reversal of this decline. Rifampicin-mediated mixed function oxidase induction appeared similar to that reported for non-vegetarians and largely persists with combination therapy throughout treatment. Isoniazid can act as a competitive inhibitor of hepatic oxidase activity in some patients.

Topics: Antipyrine; Diet, Vegetarian; Drug Therapy, Combination; Enzyme Induction; Female; Half-Life; Humans; Hydrocortisone; India; Isoniazid; Liver; Male; Mixed Function Oxygenases; Quinine; Rifampin; Streptomycin; Tuberculosis