Kinetics of intravenously dosed cortisol in four men. Consequences for calculation of the plasma cortisol production rate.

The kinetics of cortisol in the serum of 4 healthy men were studied following single i.v. doses of 2 and 0.8 mg of cortisol. The disappearance of cortisol was determined by blood sampling frequently over 2.5 h and analysing the apparently biexponential cortisol decay. The main results, shown as the mean (+/-SD), were: (a) the average distribution volume of cortisol at steady state (Vd,ss), which was 7.1 l/m2 body surface area. The extrapolated distribution volume (Vd,ext) was 8.4 l/m2, being 18% higher than the corresponding Vd,ss. (b) It was confirmed that plasma cortisol disappears biexponentially. Since the rapid phase remains unnoticed if cortisol is measured at an interval of 10 or more minutes, the obscured rapid-phase parameters can be found only if the known ratio of the two rate constants is used. (c) The fraction of cortisol, which during this fast phase irreversibly disappeared 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, namely t1/2(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 3H/m2). All urine was collected in 15 portions during the next 3 days, followed by measuring the cumulative radioactivity and analysing the triexponential increase of urinary radioactivity [1]. The main results with the urinary model were: (a) the half-life of cortisol elimination from the circulation was 40 +/- 11 min, (b) the maximal radioactivity (69 +/- 7% of the dose) in the first pool (liver) was 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 concentrations in plasma to fit a monoexponential function, allowed us to compare the half-life of cortisol decay with that from the urinary model. It was found that these half-lives were similar with values between 30 and 40 min. Finally, the distribution volume has to be measured individually if a 24 h plasma cortisol profile is used for the calculation of the cortisol production rate.