PT  - JOURNAL ARTICLE
AU  - Le Doze, François
AU  - Debruyne, Daniele
AU  - Albessard, Françoise
AU  - Barre, Louisa
AU  - Defer, Gilles Louis
TI  - Pharmacokinetics of All-<em>trans</em> Retinoic Acid, 13-<em>cis</em> Retinoic Acid, and Fenretinide in Plasma and Brain of Rat
DP  - 2000 Feb 01
TA  - Drug Metabolism and Disposition
PG  - 205--208
VI  - 28
IP  - 2
4099  - http://dmd.aspetjournals.org/content/28/2/205.short
4100  - http://dmd.aspetjournals.org/content/28/2/205.full
SO  - Drug Metab Dispos2000 Feb 01; 28
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