Differences in the pharmacokinetics of 13-CIS retinoic acid in cancer patients

✍ Scribed by A.R. Waladkhani; M.R. Clemens

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 35 KB
• Volume: 70
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19970207)70:4<494::aid-ijc24>3.0.co;2-e

✦ Synopsis

Pharmacokinetic studies of 13-cis retinoic acid (13cRA) and all-trans retinoic acid (ATRA), the 2 most commonly used retinoids, have suggested significant differences in the disposition of these compounds despite their structural similarity. In vivo treatment with 13cRA has been associated with 20-30% isomerization to ATRA (Brazzel and Colburn, 1982). Metabolism of retinoic acid (RA) occurs via a cytochrome P-450-mediated enzyme system in tissues such as the liver (Frolik et al., 1979;Leo et al., 1984), the trachea (Frolik et al., 1979) and the intestinum (Roberts et al., 1979). The primary product is 4-OH RA, which is further transformed to 4-oxo RA. After isomerization to 4-oxo-13cRA (Zile et al., 1982) and glucuronidation (Dunagin et al., 1966;Zile et al., 1982), this metabolite, like other metabolites, is excreted in the bile (Zile et al., 1982). The present study was performed to examine the pharmacokinetic characteristics of 13cRA in healthy volunteers and of 13cRA in combination with interferon (IFN)-a in patients suffering from squamous-cell carcinomas of the cervix and the head and neck.