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M D Melgar

Publications and source records attributed to M D Melgar.

At least 19 recordsLinked to original sources
PubMed1976

Metabolism of 3-(hydroxymethyl)-8-methoxychromone in the rat. II. Classification and identification of urinary drug metabolites.

1. Five metabolites were isolated from the urine of dogs dosed with 3-(hydroxymethyl)-8-methoxy[4-14C]chromone. These were identified as 8-methoxychromone, 2-hydroxy-3-methoxyacetophenone, 3-(hydroxymethyl)-8-hydroxychromone, 8-hydroxychromone and 2,3-dihydroxyacetophenone. 2. These compounds were also present in the urine of rats treated with labelled drug, together with unchanged drug and two intermediate metabolites, 3-carboxy-8-methoxychromone and 3-(carboxymethyl)-8-hydroxychromone. 3. In addition to the unconjugated labelled compounds, glucuronides and sulphates were identified. 4. Quantitative data were obtained for all of the 20 labelled compounds in rat urine. 5. A scheme is presented for the biotransformation of 3-(hydroxymethyl)-8-methoxychromone in rats and dogs, and a mechanism for scission of the gamma-pyrone ring is suggested.

Animals↗
PubMed1975

Pentaerythritol tetranitrate and metabolites in rat plasma.

Intact pentaerythritol (PE) tetranitrate and all seven of its metabolites were present in blood withdrawn from the hearts of rats dosed by gavage with 14-C-PE tetranitrate (10 mg/kg). The plasma half-life (T 1/2) of PE tetranitrate was 2 hours which is far longer than the rat T 1/2 values of all other organic nitrates in clinical use. PE trinitrate, the obligatory metabolite of PE tetranitrate now in clinical trial, establishes much higher plasma levels and has a longer T 1/2 (3 hours) than its parent drug. PE trinitrate glucuronide acts as a reservoir for its aglycone and remains in blood for 48 hours after PE tetranitrate administration.

Animals↗
PubMedDate not supplied

Tracazolate metabolites in rat tissue.

Tracazolate (4-n-butylamino-1-ethyl-6-methyl-1H-pyrazolo[3,4-b] pyridine-5-carboxylic acid ethyl ester) undergoes extensive biotransformation to lipophilic metabolites following oral dosage to male rats. Twenty-one metabolites were identified in a plasma hexane extract by mass spectrometry. Coadministration of unlabeled tracazolate with its stable carbon-13 isotope expedited the isolation and identification of 11 biotransformation products. The various metabolites resulted from either hydrolysis, oxidation, dealkylation, or conversion of an ethyl group to a vinyl group and also from combinations of these biotransformation reactions. Brain extract contained tracazolate and 12 of the metabolites found in plasma. Extracts of fat contained tracazolate and nine of the plasma metabolites. An uncommon type of metabolite less polar than tracazolate (1-vinyl tracazolate) was isolated by HPLC and identified by mass spectrometry.

Adipose Tissue↗
PubMedDate not supplied

Metabolism, disposition, and pharmacokinetics of tracazolate in rat and dog.

The metabolism, disposition, and pharmacokinetics of tracazolate, (4-butylamino-1-ethyl-6-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester), a novel anxiolytic agent, were studied in rat and dog following single oral and iv doses. Although tracazolate exhibits very good absorption (greater than 80%) in both species, it is extensively metabolized, accounting for low bioavailability. Excretion of 14C was rapid, with the kidney being the major organ of excretion. Tracazolate was not detected in the urine after iv doses even though measurable levels were found in blood, suggesting reabsorption of the compound by the renal tubules. The logarithm of the blood drug concentration vs. time data for both species was best described by a three-compartment open model. Mean t1/2 (beta) for tracazolate in the rat and dog were 14 and 10 hr, respectively. The distribution of radioactivity in rats showed that the concentrations of 14C and 14C-tracazolate were greater in tissues than in blood. Tracazolate was the predominant radioactive compound in brain during the first 6 hr and in fat for 96 hr. The extent and decay of tracazolate in fat strongly suggest that this tissue contributes significantly towards the equilibrium of drug between "deep body compartments" and blood. The major metabolite in blood was de-esterified tracazolate (ICI-US 7773) and in brain the gamma-ketotracazolate (ICI-US 10052).

Animals↗