G. Dutton
1978
Citations
1
Influential Citations
140
Citations
Quality indicators
Journal
Annual review of pharmacology and toxicology
Abstract
Drug metabolism has been divided into two successive phases (1). Phase 1 involves hydroxylation, dealkylation, hydrolysis, or similar modifications of the administered molecule. Phase 2 consists of one or more biosynthetic reactions whereby endoge nous polar molecules are conjugated with the products of Phase 1 or with the administered drug itself if it possesses a conjugable grouping. These conjugates are generally readily excreted, although certain of them are biologically active and may contribute towards further metabolism of the administered drug or its derivative (2). This review concerns developmental aspects of Phase 2 reactions, principally glucuronidation. Glucuronidation is the most important Phase 2 reaction in verte brates because of the variety of species and tissues performing it, the range of molecular structures glucuronidated, and the net amount of conjugate formed (3). We concentrate on significant advances in the field and whenever possible on the natural mechanisms regulating perinatal development of Phase 2 reactions. Refer ences cannot be comprehensive; for general aspects, reviews are preferentially listed, including the excellent surveys in this series (4-7), which discuss many studies of conjugation not duplicated here. Development in Phase 1 has been recently well covered (8). Literature was examined up to January 1977; a few outstanding later contribu tions are included, and unpublished information kindly made available subsequently is added to the reference list. The conjugation reactions treated ,are (a) glucuronidation, (b) other glycosyla tions, (c) sulfation, (d) acetylation, (e) conjugation with amino acids, (j) conjuga tion with glutathione, and (g) methylation. These reactions are virtually all deficient