Biotransformation in vivo

Although drug biotransformation in vivo can occur by spontaneous, noncatalyzed chemical reactions, most transformations are catalyzed by specific cellular enzymes. At the subcellular level, these enzymes may be located in the endoplasmic reticulum (ER), mitochondria, cytosol, lysosomes, or even the nuclear envelope or plasma membrane. 

LC-MS-based procedures for chiral and enantioselective analysis of mammalian samples are discussed in the Sects. 3.2 and 3.2.2 [47-50], Detailed data on biotransformation in vivo especially in man are quite rare. LC-ESI MS/MS procedures are referred that allowed metabolite identification in animals in in vivo and in vitro models [51, 52],... 

Metabolism. JM216 is rapidly biotransformed in vivo with no parent drug being detectable in any of the patient samples examined even as early as 15 min post administration [26]. Six platinum-containing peaks were observed in patient s plasma ultrafiltrate samples [26], Initially, metabolic studies were performed in fresh human plasma incubated with JM216 and... 

The mechanism of the species-specific action of thalidomide is not known. The compound crosses the placenta and has similar pharmacokinetic parameters in susceptible species (rabbit) and resistant species (rodent). The molecular structure of thalidomide and requirements for malformation are very specific. Thalidomide decomposes rapidly in water to at least 12 different products - all of which are inactive as teratogens and all of which undergo biotransformation in vivo to other products. These data... 

The metabolism of plants has been followed extensively using various NMR techniques, employing P, and nuclei. All kinds of samples, cells, tissues, and extracts, both in vivo and in vitro, have been investigated. A special hardware design is used for following biotransformations in vivo. Thus the living material is suspended in a culture medium in the NMR tube and air is bubbled through a capillary tube to maintain life. 

In Vivo Monitoring of Metal Biotransformations in Environmental Matrices... 

Kassahun, K. Pearson, P. G. Tang, W. McIntosh, I. Leung, K. Elmore, C. Dean, D. Wang, R. Doss, G. Baillie, T. A. Studies on the metabolism of troglitazone to reactive intermediates in vitro and in vivo. Evidence for novel biotransformation pathways involving quinone methide formation and thiazolidinedione ring scission. Chem. Res. Toxicol. 2001, 14, 62-70. 

Ghanayem Bl, Ahmed AE. 1982. In vivo biotransformation and biliary excretion of 1-14C-acrylonitrile in rats. Arch Toxicol 50 175-185. 

Halpin RA, Ulm EH, Till AE, et al. Biotransformation of lovastatin.V. Species differences in in vivo metabolite profiles of mouse, rat, dog, and human. Drug Metab Dispos 1993 21(6) 1003-1011. 

Studies on the metabolism of troglitazone to reactive intermediates in vitro and in vivo. Evidence for novel biotransformation pathways involving quinone methide formation and thiazolidinedione ring scission. Chemical Research in Toxicology, 14 (1), 62—70. 

Clark DE. 1977. The effect of hexachlorobenzene on in vivo biotransformation, residue deposition, and elimination of certain exogenous compounds and on body weight and organ weight in the rat. Dissertation Abstracts International B-The Sciences and Engineering 37(12 Pt.1) 6087-B. 

Although the metabolism of several phthalate esters has been studied in vitro, essentially all of the in vivo studies have involved DEHP. A summary of these experiments which involved exposure offish to aqueous - C-DEHP is presented in Table IV (11,12). Tissue C was isolated and separated into parent and the various metabolites by preparative thin layer chromatography on silica gel. Metabolites were hydrolyzed where appropriate and identified by gas chromatography-mass spectroscopy. In whole catfish, whole fathead minnow and trout muscle, the major metabolite was the monoester while in trout bile the major metabolite was the monoester glucuronide. The fact that in all cases the major metabolite was monoester or monoester glucuronide despite the differences in species, exposure level and duration, etc. represented by these data, suggests that hydrolysis of DEHP to monoester is important in the biotransformation of DEHP by fish. 

Despite all the problems attendant on studies of aquatic animals, however, great strides have been made in the past 10 years in defining biochemical pathways used by fishes to biotransform and eliminate xenobiotics (2, 3, 4, 5). Many of the earlier studies, especially the extensive work of DeWaide (6), defined various biochemical transformations which xenobiotics may undergo in vitro. Only in the past 10 years have in vivo studies been undertaken to define the routes and rates of elimination of xenobiotics by fishes (7, 8, 9, 10, ll). 

In vitro demethylation of aminopyrine by fish liver preparations was reported by DeWaide (6). Olson et al. (32) showed the in vivo stepwise N-dealkylation of the herbicide, N3,N3-diethyl-2,4-dinitro-6-tri fluoromethyl-ra-phenylenediamine (dinitramine), by carp (Figure 1). Biotransformation products were found in... 

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