An investigation of the dose proportionality of deflazacort pharmacokinetics.
The dose proportionality of deflazacort was assessed following single-dose oral administration at doses of 3, 6, and 36 mg to 24 healthy young adult volunteers. The active metabolite of deflazacort (21-desacetyl deflazacort) was monitored in plasma using a sensitive, semi-microbore liquid chromatographic method. Cmax averaged 10.4 +/- 5.0, 19.8 +/- 7.5, and 132.6 +/- 52.5 ng mL-1 for the 3, 6, and 36 mg doses, respectively. AUC(0-infinity) averaged 38.5 +/- 37.1, 64.9 +/- 20.8, and 411.7 +/- 148.5 ng h mL-1 for the same three doses, respectively. Elimination half-life ranged from 1.9 +/- 0.5 h at the 6 mg dose to 2.4 +/- 1.5 h at the 36 mg dose. Regression analyses of dose versus Cmax and AUC(0-infinity) yielded intercepts which were not significantly different from zero (p > 0.05) and slopes which were significant (p < 0.05). Regression analysis of dose versus apparent oral clearance yielded a slope which was not significantly different from zero (p > 0.05). These data indicate that deflazacort exhibits dose-proportional pharmacokinetics.
Rao
N
N
Department of Clinical Pharmacokinetics, Hoechst Marion Roussel, Kansas City, MO 64137, USA.
Bhargava
V O
VO
Reynolds
D L
DL
Eller
M G
MG
Weir
S J
SJ
D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D011282:Pregnenediones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015203:Reproducibility of Results
D000893:Anti-Inflammatory Agents; D011282:Pregnenediones; C021988:deflazacort