Desethyl

N-desethyl) (5-hydroxymethyl) Sign, altered in renal via CYP4503A4 (polymorphic... 

Evidently, due to the cross-reactivity of both mono- and di-desethyl metabolites, a specific assay of flurazepam could not be developed successfully without first separating it from its metabolites effectively by the help of column chromatography. 

The hydrolysis half-lives at pH 7.4 and 20 and 37.5 °C were 130 and 27 d, respectively. At pH 6.1 and 20 °C, the hydrolysis half-life was 170 d (Freed et al, 1979). When equilibrated with a prereduced pokkali soil (acid sulfate), parathion instantaneously degraded to aminoparathion. The quick rate of reaction was reportedly due to soil enzymes and/or other heat labile substances. Desethyl aminoparathion was also identified as a metabolite in two separate studies (Wahid and Sethunathan, 1979 Wahid et al., 1980). The half-lives for the degradation of parathion in a silty clay (pH 5.5) and sandy clay (pH 6.9) were 23 and 22 d, respectively (Sattar, 1990). 

Surface Water. Desethyl- and desisopropylatrazine were degradation products of atrazine identified in the Mississippi River and its tributaries (Pereira and Rostad, 1990). Under laboratory conditions, atrazine in distilled water and river water was completely degraded after 21.3 and 7.3 h, respectively (Mansour et al., 1989). 

Because each herbicide may degrade during volatilization, it is interesting to compare the cumulative volatilization of the parent contaminant and its metabolites. This behavior was studied in a wind-tunnel experiment by Wolters et al. (2003) for a mixture of parathion, terbuthylazine, and fenpropimorph, as well as for the metabolites fenpropimorph acid and desethyl-tetrabuthylazine. Figure 8.6... 

Coupling of other vindoline derivatives with ring D or E modified oxidation levels (92-96) to catharanthine N-oxide provided new binary products for biological evaluation 39, 95-97). The two diastereomeric C-16 -C-14 PARE anhydrovinblastines 42 and 97 were obtained in a 46 54 ratio (50% yield) from racemic catharanthine (98), and the corresponding 20 -desethyl compounds 98 and 99 were generated at - 20°C in a 1 1 ratio (16% yield each), and at -76°C in lower yields, together with the corre-... 

Determination of brinzolamide and its 3 principal metabolites (the N-desethyl, A -desmethoxypropyl and O-desmethyl analogs) in whole blood and plasma from clinical and pre-clinical studies was performed using high performance liquid chromatography (HPLC) with UV detection. After addition of a known amount of internal standard (AL-5138, the 4-methoxybutyl analog of brinzolamide), the sample was acidified with 50 mM sodium phosphate buffer, pH 3.0 and extracted with ethyl acetate. 

Primary metabolic pathways of brinzolamide include formation of the N-desethyl, A-desmethoxypropyl and 0-desmethyl analogs, all of which are... 

In humans, only the jV-desethyl metabolite is detected in whole blood, although trace amounts of the other two metabolites are found in urine. All three of the above exhibit binding to carbonic anhydrase and prolonged half-lives in whole blood. In rats, a carboxylic acid metabolite formed by oxidation of the O-desmethyl analog is the predominant urinary metabolite. Small amounts of this compound are also found in human urine. 

A procedure for the determination of dorzolamide and its desethyl metabolite in biological fluids has been described using HPLC and UV detection at 252 nm [13]. The limit of detection for both compounds was 5 ng/mL in whole blood, plasma, and urine. 

In vitro studies indicated that dorzolamide binds strongly to erythrocyte carbonic anhydrase CA II and very weakly to CA I. The desethyl metabolite also binds to both CA I and CA II, but has less affinity for CA II and is considerably less selective for CA II than dorzolamide. 

In man, dorzolamide is metabolized by A-deethylation. Sensitive HPLC assays for both entities in whole blood, plasma, and urine have been developed to support clinical pharmacokinetic studies [13]. Both the parent compound and /V-desethyl-dorzolamide are excreted in the urine. 

At steady state, renal excretion was 1.3 mg/day of the total daily dose of 4 mg, and the renal clearance was 90 mL/min. Unchanged dorzolamide accounts for about 80 % of the total urinary excretion, and A-desethyl-dorzolamide accounts for the remaining 20% [16]. 

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