Terminal metabolite, common

Oxidation of divalent sulfur atoms in thioethers is a common biotransformation of sulfur-containing compounds [Eq. (9)]. Oxidation proceeds in two stages, first to the sulfoxide and then to the sulfone. Sulfoxides have increased polarity and are often observed as excreted metabolites, but they can also be reduced back to the sulfide. Formation of the sulfoxide creates an asymmetric center, and stereospecific oxidation can occur. Sulfones tend to be terminal metabolites no evidence for their reduction exists. 

The common terminal metabolite of a glutathione conjugate In a mammal Is a mercapturlc acid —-an N-acetyl- -substltuted-L-cystelne. The equivalent In the plant the phytomercapturlc acid — Is an N-malonyl- -substltuted-L-cystelne (Figure 3). The susceptibility of the -malonyl group to hydrolysis In the mammal has not, to our knowledge, been studied. If It Is stable then the phytomercapturlc acid Is likely to be eliminated unchanged (or perhaps S oxldlzed). 

The common C-terminal amino acid sequence required for exerting activity at tachykinin receptors is shown in bold endokinin C and D lack the C-terminal Met and are almost devoid of affinity at these receptors. In red, the sequence of neurokinin A of which neuropeptide-gamma and neuropeptide-kappa are elongated forms and neurokinin A (3-10) is a product of beta or gamma-TAC1 mRNAs or an NKA metabolite active at tachykinin receptors. In blue, the sequence of human HK-1 of which endokinin A and B are elongated forms. 

Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinases inhibitor approved for use in patients with chronic myelogenous leukemia after ima-tinib treatment and for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Maximum plasma concentrations (Cmax) of dasatinib are observed between 0.5 and 6 hours (Tmax) following oral administration. Dasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4. CYP3A4 was the primary enzyme responsible for the formation of the active metabolite. The overall mean terminal half-life of dasatinib is 3-5 hours. Adverse events included mild to moderate diarrhea, peripheral edema, and headache. Neutropenia and myelosuppression were common toxic effects. 

The most commonly encountered side effects of sodium nitroprusside administration are nausea, vomiting, and headache, which quickly dissipate when the infusion is terminated. When sodium nitroprusside treatment extends for several days, there is some danger of toxicity owing to the accumulation of its thiocyanate metabolite. Thiocyanate intoxication includes signs of delirium and psychosis hypothyroidism also may occur. If nitroprusside is administered for several days, thiocyanate levels should be monitored. 

Osteitis fibrosa does not occur, as in renal osteodystrophy. The common features that appear to be important in this group of diseases are malabsorption of calcium and malabsorption of vitamin D. Liver disease may, in addition, reduce the production of 25(OH)D from vitamin D, although its importance in all but patients with terminal liver failure remains in dispute. The malabsorption of vitamin D is probably not limited to exogenous vitamin D. The liver secretes into bile a substantial number of vitamin D metabolites and conjugates that are reabsorbed in (presumably) the distal jejunum and ileum. Interference with this process could deplete the body of endogenous vitamin D metabolites as well as limit absorption of dietary vitamin D. 

The tricyclic antidepressants typically undergo multiple routes of metabolism. The most common, depending on the particular ring system, are N-demethylation of the terminal amine, aromatic hydroxylation, and benzylic or "bridge" hydroxylation (see Table 8.7). In general, with the exception of the secondary amine metabolites of iV AT-dimethyl-amino TCAs, the metabolites are usually less active or inactive as antidepressants. 

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