Metabolites conjugate

MAE in conjunction with high-performance liquid chromatography/mass spectrometry (HPLC/MS) shortened the cleanup procedure and provided satisfactory recoveries (97-102%) for the parent imazethapyr and its two metabolites (hydroxy and glucose conjugate metabolites). 

Walle, U. K., Galijatovic, A., Walle, T., Transport of the flavonoid chrysin and its conjugated metabolites by the human intestinal cell line Caco-2, Biochem. Pharmacol. 1999, 58, 431-438. 

Tang, W. and Abbott, F.S. 1996. Characterization of thiol-conjugated metabolites of 2-propylpent-4-enoic acid (4-ene VPA), a toxic metabolite of valproic acid, by electrospray tandem mass spectrometry. J. Mass Spectrom. 31 926. 

In recent years, using both thin-layer chromatography (TLC) and high-pressure liquid chromatography (HPLC), it has been possible to separate and identify a variety of conjugated and non-conjugated metabolites of aromatic hydrocarbons in marine organisms (8,10,12,15,42,43,44). 

Recent studies in our laboratories have shown that newly hatched herring (Clupea harengus pal Iasi) larvae exposed to purififed 3H-naphthalene in seawater at concentrations of 10 ppb for 9 hr accumulated a variety of conjugated and non-conjugated metabolites. HPLC analysis indicates the presence of the parent compound as well as three additional compounds whose retention times are consistent with a sulfate, a dihydrodiol, and 1-naphthol (Fig. 3). 

Lactam formation has been documented for a few drugs or drug metabolites. For example, the in vivo formation of a primary lactam metabolite was reported for bromfenac and perindopril. Bromfenac (11.144) is an anti-inflammatory agent, which, in humans and monkeys, is cyclized to the lactam 11.145, the first metabolite to appear in urine [159], At later times post-dose, hydroxylated and conjugated metabolites of 11.145 are excreted. Thus, cy-clization by dehydration appears to be the major if not the sole primary re-... 

The analysis of codeine, morphine, 6-monoacetylmorphine (6-MAM, a metabohte of heroin), and cocaine is important for many toxicology labs to determine illicit drug use. When analyzing opiates in urine samples, frequently the matrix chosen for drug screening, the conjugated metabolites must be hydrolyzed however, this process can break down 6-MAM (Christophersen et al., 1987). These compounds can be derivatized to increase sensitivity, and both BCD and NPD are used for these assays. Derivatizations used include reaction with N-methyl-N-trimethylsilyltrifluoroacetamide followed by GC-FID (Lin et al., 1994) or with N,0-bis(trimethylsilyl)trifluoroacetamide (Christophersen et al., 1987 Lee and Lee, 1991), PFPA (Christophersen et al., 1987), or heptafluorobutyric anhydride (HFBA) followed by GC-ECD. All these methods show good sensitivity and selectivity. 

Dihydralazine and minoxidil (via its sulfate-conjugated metabolite) dilate arterioles and are used in antihypertensive therapy. They are, however, unsuitable for monotherapy because of compensatory circulatory reflexes. The mechanism of action of dihydralazine is unclear. Minoxidil probably activates K channels, leading to hyperpolarization of smooth muscle cells. Particular adverse reactions are lupus erythematosus with dihydralazine and hirsutism with minoxidil—used topically for the treatment of baldness (alopecia androg-enetica). 

Rimantadine is well absorbed following oral administration, with peak blood levels achieved in 5 to 7 hours. Its elimination half-life averages 25 hours in young adults and 32 hours in the elderly. Less than 25% of the dose is excreted in the urine as unchanged drug the remainder is eliminated as hydroxylated or conjugated metabolites. 

Doxorubicin is not absorbed orally, and because of its ability to cause tissue necrosis must not be injected intramuscularly or subcutaneously. Distribution studies indicate rapid uptake in all tissues except the CNS. Extensive tissue binding, primarily intranuclear, accounts for the prolonged elimination half-life. The drug is extensively metabolized in the liver to hydroxylated and conjugated metabolites and to aglycones that are primarily excreted in the bile. 

It is readily absorbed from the GI tract, extensively bound to plasma proteins and excreted mainly in the urine as unchanged drug or conjugated metabolites. 

Levodopa is excreted in the urine as conjugated metabolites and its main metabolite is homo vanillic acid (HVA). 

Correction of the metabolic acidosis with intravenous bicarbonate. This will also increase urine flow and cause it to become more alkaline (alkaline diuresis) and therefore facilitate excretion of salicylic acid and its conjugated metabolites. As the blood pH rises, the ionization of the salicylic acid increases, causing a change in the equilibrium and distribution of salicylate, which diffuses out of the CNS (Fig. 7.59). 

Nabumetone is well absorbed from the gastrointestinal tract following oral administration and undergoes rapid and extensive first-pass metabolism in the liver to 6-MNA and other inactive metabolites. There is 99% binding of 6-MNA to plasma protein and it has an elimination half-life of up to 22 h with marked individual differences. 6-MNA is metabolized by O-methylation and conjugation and is excreted to about 80% in the urine as inactive or conjugated metabolites (Davies, 1997). 

Steroid hormones are generally converted into inactive metaboic excretion products in the liver. Reactions include reduction of unsaturated bonds and the introduction of additional hydroxyl groups. The) resulting structures are made more soluble by conjugation with curonic acid or sulfate (from PAPS, see p. 160). Approximate ) twenty to thirty percent of these metabolites are secreted into the bile and then excreted in the feces, whereas the remainder ae t released into the blood and filtered from the plasma in the kidney, passing into the urine. These conjugated metabolites are fairb1 water-soluble and do not need protein carriers. 

Alprazolam, a triazolobenzodiazepine, is also extensively metabolized by oxidation and conjugation. Metabolites include a-hydroxyalprazolam, 4-hydroxyalprazolam, and a,4-dihydroxyalpra-zolam. The first two metabolites possess approximately 66 and 19% of the pharmacological activity... 

Silberberg M, Morand C, Mathevon T, Besson C, Manach C, Scalbert A, Remesy C. 2006. The bioavailability of polyphenols is highly governed by the capacity of the intestine and of the liver to secrete conjugated metabolites. Eur J Nutr 45 88-96. 

Potential Health Effects of Conjugated Metabolites at Target Sites 191... 

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