Prednisolone pharmacokinetics and pharmacodynamics in relation to sex and race

Prednisolone pharmacokinetics (PK) and pharmacodynamics (PD) were investiga ted in relation to sex and race in white males, black males, white females, and black females (n = 8/group) after a single oral dose (0.27 mg/kg) of p rednisone. The study consisted of baseline and prednisone phases with 32-ho ur sampling in each phase. Women were studied during the luteal phase of th eir menstrual cycle. Total and free plasma prednisolone concentrations were assayed by HPLC and ultrafiltration, and pharmacokinetic data were analyze d by compartmental fitting using WinNonlin. Plasma cortisol concentrations were assayed by HPLC; T-helper, T-suppressor lymphocyte, and neutrophil cel l counts were determined by FACS and hemocytometry, and these pharmacodynam ic data were evaluated by basic and extended indirect response models using ADAPT II. Total body weight-normalized free prednisolone oral clearance an d apparent volume of distribution were higher in men compared with women, r egardless of race (by 22% in whites and 40% in blacks for oral clearance, p < 0.01; by 32% in whites and 38% in blacks for apparent volume of distribu tion, p < 0.01). The 50% inhibitory concentration (IC50) values for T-suppr essor cell-trafficking inhibition were higher in whites than in blacks, reg ardless of sex (by 125% in men and 208% in women, p < 0.01). The IC50 or SC 50 values for effects of prednisolone on cortisol secretion and T-helper ly mphocyte or neutrophil trafficking were not statistically different between men and women, blacks and whites. The findings of this study suggest that there are some prednisolone PK/PD differences related to sex and race. Howe ver, these differences do not suggest the need for dosage adjustments, and additional experiments with repeat dosing are needed to fully evaluate the clinical implication of these findings.