KINETICS OF INTRAVENOUSLY DOSED CORTISOL IN 4 MEN - CONSEQUENCES FOR CALCULATION OF THE PLASMA-CORTISOL PRODUCTION-RATE

The kinetics of cortisol in the serum of 4 healthy men were studied fo llowing single i.v. doses of 2 and 0.8 mg of cortisol. The disappearan ce of cortisol was determined by blood sampling frequently over 2.5 h and analysing the apparently biexponential cortisol decay. The main re sults, shown as the mean (+/- SD), were: (a) the average distribution volume of cortisol at steady state (V-d,V-ss), which was 7.1 l/m(2) bo dy surface area. The extrapolated distribution volume (V-d,V-ext) was 8.4 l/m(2), being 18% higher than the corresponding V-d,V-ss. (b) It w as confirmed that plasma cortisol disappears biexponentially. Since th e rapid phase remains unnoticed if cortisol is measured at an interval of 10 or more minutes, the obscured rapid-phase parameters can be fou nd only if the known ratio of the two rate constants is used. (c) The fraction of cortisol, which during this fast phase irreversibly disapp eared according to the two-compartment open model, was 5 to 8% larger than that found using the monocompartment model. (d) The half-life of the slow or beta phase was equal for the 2 and 0.8 mg experiments, nam ely t(1/2)(beta) = 66 +/- 18 min. The kinetics of cortisol in the same 4 men were also measured after an i.v. dose of radioactive cortisol ( 82 +/- 7 kBq H-3/m(2)). All urine was collected in 15 portions during the next 3 days, followed by measuring the cumulative radioactivity an d analysing the triexponential increase of urinary radioactivity [1]. The main results with the urinary model were: (a) the half-life of cor tisol elimination from the circulation was 40 +/- 11 min, (b) the maxi mal radioactivity (69 +/- 7% of the dose) in the first pool (liver) wa s found at 2 +/- 0.3 h, (c) the half-life of the cortisol metabolites in the body was 6.8 +/- 0.7 h. Forcing the measured cortisol concentra tions in plasma to fit a monoexponential function, allowed us to compa re the half-life of cortisol decay with that from the urinary model. I t was found that these half-lives were similar with values between 30 and 40 min. Finally, the distribution volume has to be measured indivi dually if a 24 h plasma cortisol profile is used for the calculation o f the cortisol production rate. (C) 1997 Elsevier Science Ltd. All rig hts reserved.