Drugs biotransformation

Type of response measured (e.g., concentration or amount of the drug or biotransformed drug)... 

B. Testa, G. Cruciani, Structure-metabolism relations and the challenge of predicting biotransformation, in Pharmacokinetic Optimization in Drug Research, B. Testa, H. van de Water-beemd, G. Folkers, R. Guy (Eds.), WHey-VCH, Weinheim, New York, 2001, pp. 65-84. 

German investigators (Brock et al) worked on the creation of alkylating pro-drugs that have cytostatic activity after specific biotransformation in the tumor tissue. Cyclophosphamide (CTX) has well pronounced antitumor activity with the broadest spectrum. It is metabolized to the cytotoxic phosphoamide mustard. In normal tissues with high enzyme level cyclophosphamide is converted to its inactive metabolites (Fig. 2). These differences in biotransformation can explain the relative selectivity of cyclophosphamide towards... 

Cytochrome P450 2D6, also termed debrisoquine-sparteine hydroxylase, is a mixed-function oxidase localized in the endoplasmic reticulum which is responsible for the biotransformation of several tricyclic antidepressants, antipsychotics, beta-blockers, opioids, and many other drugs. 

A different task was pursued by the CM of CsA with various maleates 339 [ 148]. The CM demanded in this case the highly active Hoveyda catalyst D, that exhibits potency not reached by the phosphine-containing catalysts C and E. Under the conditions given in Scheme 65, metathesis with maleates 339 led (E)-selectively to the a,/J-unsaturated ester derivatives 340 in high yield. Compounds 340 still demonstrated activity comparable to that of CsA and are thus potential soft drugs via esterase-mediated biotransformation to the corresponding inactive carboxylic acids 341. 

Further intense ions, at m/z 483, 523 and 539, were observed when the TIC data were scrutinized manually. The RICs for these ions are shown in Figure 5.43. These masses are not expected from any of the biotransformations given in Table 5.13 and indicate significantly lower molecular weights than the parent drug. 

Zhang HX, Sultatos EG. 1991. Biotransformation of the organophosphorus insecticides parathion and methyl parathion in male and female rat livers perfused in situ. Drug Metab Dispos 19 473-477. 

Anari MR, Sanchez RI, Bakhtiar R, Franklin RB, Baillie TA. Integration of knowledge-based metabolic predictions with liquid chromatography data-dependent tandem mass spectrometry for drug metabolism studies application to studies on the biotransformation of indinavir. Anal Chem 2004 76 823-32. 

Pan, M.H. et al.. Biotransformation of curcumin through reduction and glucuronida-tion in mice. Drug. Metab. Dispos., 27, 486, 1999. 

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