Prednisolone pharmacokinetics and pharmacodynamics in relation to sex and race

Prednisolone pharmacokinetics (PK) and pharmacodynamics (PD) in relation to sex and race were investigated in eight white men (WM), eight black men (BM), eight white women (WW), and eight black women (BW) after a single oral dose (0.27 mg/kg) or prednisone. The study consisted of baseline and prednisone phases with 32 hour sampling in each phase. Women were studied during the luteal phase of their menstrual cycle. Total and free plasma prednisolone concentrations were assayed by HPLC and ultrafiltration and assessed by compartmental fitting using WinNonlin. PD response-time profiles for plasma cortisol concentrations assayed by HPLC, CD4, CD8 lymphocyte and neutrophil cell counts determined by FACS and hemocytometry were evaluated by basic and extended indirect response models using Adapt II. The mean parameter estimates are presented in the following table: Parameters WM BM WW BW CL/F/TBW (L/hr/kg) 0.788 0.778 0.644 0.554 T_1/2(hr) 1.92 2.01 1.76 2.01 Cortisol IC₅₀ (ng/mL) 0.631 1.30 1.13 1.90 CD4 IC₅₀ (ng/mL) 5.05 3.22 3.90 3.38 CD8 IC₅₀ (ng/mL) 16.9 7.50 14.7 4.77 Neutrophil SC₅₀ (ng/mL) 57.7 28.4 26.9 24.9 In the above parameters, CL/F/TBW achieved significant (p<0.01) sex difference and CD8 IC₅₀ achieved significant (p<0.01) race difference. The findings of this study suggest that there are some prednisolone PK/PD differences between men and women, blacks and whites. However, these differences do not warrant a dosage adjustment based on sex and race in clinical use of prednisone.