In vitro biotransformation

In the next section, we will expand on the possibilities of using in vitro biotransformation to diversify products. 

Schlenk D, DR Buhler (1991) Role of flavin-containing monooxygenase in the in vitro biotransformation of aldicarb in rainbow trout (Oncorhyncus mykiss). Xenobiotica 21 1583-1589. 

J. Yu, E. R. Butelman, J. H. Woods, B. T. Chait, and M. J. Rreek. In Vitro Biotransformation of Dynorphin A (1-17) is Similar in Human and Rhesus Monkey Blood as Studied by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry. J. Pharmacol. Exp. Then, 279(1996) 507-514. 

Brandsma S, de Boer J, Leonards P (2011) Determination of organophosphorous flame retardants in the food web of the western Scheldt - including in vitro biotransformation. 

Yilmazer, M., Stevens, J.F., Deinzer, M.L., and Buhler, D.R., In vitro biotransformation of xanthohumol, a flavonoid from hops (Humulus lupulus), by rat liver microsomes, Drug Metab. Dispos., 29, 223, 2001. 

Erickson DA, Mather G, Trager WE, Levy RH, Keirns JJ. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. Drug Metab Dispos 1999 27(12) 1488-1495. 

In vitro biotransformation studies in pig, rat, and dog liver revealed that hydroxyl mebendazole and amino mebendazole are the main metabolites of mebendazole (24). To verify the formation in vivo of the expected metabolites in eel, wild European eels were subjected to 6, 24, and 48 h treatments (25). The results clearly indicated that mebendazole given to eels via the water was absorbed and metabolized into the hydroxyl and amino metabolites, as was also tlie case with... 

Kedderis, G.L., and J.C. Lipscomb. 2001. Application of in vitro biotransformation data and pharmacokinetic modeling to risk assessment. Toxicol. Ind. Health 17(5-10) 315-321. Kershaw T.G., T.W. Clarkson, and P.H. Dhahir. 1980. The relationship between blood levels and dose of methylmercury in man. Arch. Environ. Health 35(l) 28-36. 

Clement B, Lopian K. Characterization of in vitro biotransformation of new, orally active, direct thrombin inhibitor ximelagatran, an amidoxime and ester prodrug. Drug Metab Dispos 2003 31 645-651. 

A study of the uptake and excretion of (-l-)-tubocurarine (154) and its trimethyl derivative in the rat reported no evidence for biotransformation of either substrate in vivo or in vitro with isolated perfused livers (117). A similar study with (+ )-2,3-dehydroemetine (158) showed that although metabolism occurred in vivo to give unidentified product(s) no in vitro biotransformation was carried out by rat liver microsomes (118). 

We refer to LC-MS-based methods for a PK study [61] as well as in vitro biotransformation studies with liver microsomes [23,62],... 

We herein refer to an in vitro biotransformation study in human liver microsomes [82] and a PK study in man [83] both analysed by LC-MS-based methods. 

Accordingly, Chen et al. performed a serious number of charming in vivo and in vitro biotransformation studies for diverse TTA (anisodamine, anisodine, atropine, scopolamine) after oral administration of the drugs to rat [5-7,51, 52,87], Urine was analysed by LC-MS/MS methods that provided the following operation modes ... 

Several databases of published biotransformations are commercially available, such as Molecular Design Ltd s Metabolite and the Accelerys Metabolism Database (formerly produced by Synopsis). The former is quite extensive, and contains in vivo and in vitro biotransformation summaries from the literature, while the latter has as its core information based on the U.K. Royal Society of Chemistry s Biotransformations series (Hawkins, 1988-1996) supplemented by additional data from the literature. Both systems are searchable by reaction type. The intelligent use of such databases provides much valuable information on likely metabolic profile. 

Boon et al. studied the in vitro biotransformation capacity of hepatic micro-somes of a sperm whale (Physeter macrocephalus), a white-beaked dolphin (Lagenorhynchus albirostris), a harbor seal (Phoca vitulina), and an eider duck... 

Surapaneni SS, Clay MP, Spangle LA, Paschal JW, Lindstrom TD. In vitro biotransformation and identification of human cytochrome P450 isozyme-dependent metabolism of tazofelone. Drug Metab Dispos 1997 25 1383-8. 

Interestingly, our previously described studies concerning the in vitro biotransformation of aryl azides in murine microsomes [93] generally parallel the above results observed for the chemical reduction of azides by thiols, with electron-deficient aryl azides also undergoing metabolic reduction much more rapidly than their electron-rich counterparts or alkyl azides. These similarities have led us to speculate that a possible mechanism for the enzyme-catalyzed reduction of aryl azides may entail analogous initial attack by a sulphydryl group at the active site of the appropriate enzyme, although this hypothesis remains to be confirmed. 

In vitro application of HbpA (and monooxygenases in general) offers some advantages over whole-cell biotransformations. For example, toxic effects on cell metabolism and further metabolization of the desired product can be avoided, and experimentally demanding in vivo set-ups are not necessary (beneficial for organic chemists). The major challenge in in vitro biotransformations is the efficient... 

Ishii, Y. Mukoyama, H. Ohtawa, M. In vitro biotransformation of finasteride in rat hepatic microsomes. Isolation and characterization of metabolites. Drug Metab.Dispos., 1994, 22, 79-84... 

Warrington, J.S., R.I. Shader, L.L. von Moltke, and D.J. Greenblatt (2000). In vitro biotransformation of sildenafil (Viagra) Identification of human cytochromes and potential drug interactions. Drug Metab. Dispos. 28, 392-397. 

Nielsen SE, Breinholt V, Justesen U, Cornett C, Dragsted LO. In vitro biotransformation of flavonoids by rat liver microsomes. Xenobiotic 1998 28 389-401. 

Clineschmidt, et. al. (10, 11) studied the in vitro biotransformation as well as the in vivo metabolism of C -phenelzine in rats. Phenylacet-ic acid was identified as the major metabolite. 

Bidstrup TB, Bjornsdottir I, Sidelmann UG, Thomsen MS, Hansen KT. CYP2C8 and CYP3 A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide. Br J Clin Pharmacol 2003 56 305-314. 

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