Prednisolone pharmacokinetics and pharmacodynamics in relation to sex and race.
Prednisolone pharmacokinetics (PK) and pharmacodynamics (PD) were investigated 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 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 pharmacokinetic data were analyzed by compartmental fitting using WinNonlin. Plasma cortisol concentrations were assayed by HPLC; T-helper, T-suppressor lymphocyte, and neutrophil cell counts were determined by FACS and hemocytometry, and these pharmacodynamic data were evaluated by basic and extended indirect response models using ADAPT II. Total body weight-normalized free prednisolone oral clearance and apparent volume of distribution were higher in men compared with women, regardless of race (by 22% in whites and 40% in blacks for oral clearance, p < 0.01; by32% in whites and 38% in blacks for apparent volume of distribution, p < 0.01). The 50% inhibitory concentration (IC50) values for T-suppressor cell-trafficking inhibition were higher in whites than in blacks, regardless of sex (by 125% in men and 208% in women, p < 0.01). The IC50 or SC50 values for effects of prednisolone on cortisol secretion and T-helper lymphocyte 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. However, 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.
Magee
M H
MH
Clinical Pharmacokinetics Laboratory, Kaleida Health, Millard Fillmore Hospital, State University of New York at Buffalo, USA.
Blum
R A
RA
Lates
C D
CD
Jusko
W J
WJ
D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D044383:Black People; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects; D011239:Prednisolone / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D012737:Sex Factors; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D044465:White People
D000893:Anti-Inflammatory Agents; D011239:Prednisolone; D006854:Hydrocortisone