Abstract
To determine the efficiency of conversion as a function of dose, relative amount of the biologically active metabolite of cortisone (E), hydrocortisone (F), available in systemic circulation was determined following the oral administration of 5 and 50 mg of E containing 1 to 6 uc 14C-E. 26 studies were done: 8 well subjects; 7 children, adrenogenital syndrome; 5, growth hormone deficiency; 2, Crohn's disease. Plasma concentrations of F were determined by liquid scintillation counting following TLC separation using silica gel HF-254 and a solvent system of methylene chloride-ethanal (90-10). Relative fraction of F which reaches the systemic circulation was estimated by using the area under the plasma concentration time curve normalized for differences in the radioactive dose and surface area of the subject. (AUC'). AUC' values of F for 50 mg E given i.v. is only slightly greater than when 50 mg E was given orally, but the F to E ratio was much greater by the oral route indicating a greater preponderance of the E to F conversion pathway during the absorptive phase. Mean normalized AUC values (in units of percent radioactive dose, liter-1, min.) for 5 and 50 mg dose were 283.5 (SD±104.7) and 157.8 (SD±80.6) respectively, (p-<0.001)indicating almost a 50% difference in conversion efficiencies at two doses.
Conclusion: Conversion of E to F is dose-dependent at 5 to 50 mg dosage range apparently due to saturable enzymes in the gut and liver and/or saturable transcortin binding during the absorptive phase. For those patients in whom a precise amount of F is needed, we recommend that E not be prescribed.
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Barr, W., Aceto, T. & Rider, J. 278 PHARMACOKINETIC ANALYSIS OF DOSE DEPENDENT CONVERSION OF CORTISONE TO CORTISOL. Pediatr Res 12 (Suppl 4), 410 (1978). https://doi.org/10.1203/00006450-197804001-00283
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DOI: https://doi.org/10.1203/00006450-197804001-00283