TY - JOUR 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 SP - 205 LP - 208 VL - 28 IS - 2 AU - François Le Doze AU - Daniele Debruyne AU - Françoise Albessard AU - Louisa Barre AU - Gilles Louis Defer Y1 - 2000/02/01 UR - http://dmd.aspetjournals.org/content/28/2/205.abstract N2 - 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 ER -