Effect of hydrocortisone on plasma tyrosine concentration and lymphocyte counts in healthy volunteers

Objective: During corticosteroid therapy, plasma tyrosine levels are lowere d after induction of tyrosine aminotransferase. Lymphocytopenia is consider ed to be a nongenomic effect of corticosteroids. The objective of this stud y was to test the hypothesis that both genomic and nongenomic effects of hy drocortisone (HC) can be described by essentially the same physiological mo del by pharmacokinetic-pharmacodynamic (PK/PD) modelling. Methods: Seven healthy individuals were studied for two 24-hour periods dur ing which they received either no drug or 300 mg HC orally. Results: Plasma tyrosine levels decreased by a mean maximum of 15% on the c ontrol day and by 50% on the test (HC) day. Lymphocyte counts decreased by a mean maximum of 30% on the control day and by 75% on the test day. Tyrosi ne nadirs were seen on average 2 hours later than those of lymphocyte count s. The mean estimated plasma concentration of HC that gives 50% of the maxi mum attainable drug effect (EC50) was 378 +/- 186 mg/L for increased plasma tyrosine levels. The plasma concentration giving 50% lymphocyte inhibition (IC50) was 142 +/- 42 mg/L. The effects on the control day could be fitted to essentially the same physiological model, with identical parameter valu es, as on the HC day. Conclusions: Spontaneous diurnal variation in levels of plasma tyrosine and lymphocyte counts under controlled conditions can be described by fluctuat ions in endogenous levels of HC (cortisol). These effects may be used as an indicator of the actions of exogenous corticosteroids, which may allow the study of concentration dependencies of genomic and nongenomic effects for a variety of corticosteroids.