RT Journal Article
SR Electronic
T1 Pharmacokinetics of All-<em>trans</em> Retinoic Acid, 13-<em>cis</em> Retinoic Acid, and Fenretinide in Plasma and Brain of Rat
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 205
OP 208
VO 28
IS 2
A1 Le Doze, François
A1 Debruyne, Daniele
A1 Albessard, Françoise
A1 Barre, Louisa
A1 Defer, Gilles Louis
YR 2000
UL http://dmd.aspetjournals.org/content/28/2/205.abstract
AB We have measured the pharmacokinetics of three retinoids, all-trans retinoic acid, 13-cis retinoic acid, and fenretinide in rat blood and rat brain [especially white matter (WM) and gray matter (GM)] to help select retinoids for treating human malignant glioma. All-trans retinoic acid permeated well into the WM, giving peak concentration in WM of 25.7 μg/g, 6 to 7 times higher than the peak serum concentration. There was less 13-cis retinoic acid in WM: area under the curve (AUC)0→∞ WM/AUC0→∞serum = 18.00 μg ml−1 h/32.67 μg ml−1 h. The ratio WM/GM was over 1 for these two compounds, but the half-lives were short in the serum and cerebral tissue (0.57–1.02 h). Fenretinide had different pharmacokinetics: the peak concentrations were in serum (1.7 μg/ml) and WM (1.2 μg/ml)–low, but the AUC0→∞ was large (25.55 μg ml−1 in serum and 57.53 μg ml−1 in WM) due to its long elimination half-life (13.78 h in serum and 17.77 h in WM). These findings provide information that may be used to select a retinoid and establish therapeutic regimens that provide optimal efficacy with minimal toxicity. The American Society for Pharmacology and Experimental Therapeutics