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Biomedical subjects

C E Inturrisi

Publications and source records attributed to C E Inturrisi.

At least 145 records · Page 8Linked to original sources
PubMed1975

Simultaneous determination of acetylmethadol and its active riotransformation products in human biofluids.

A method employing solvent extraction and gas-liquid chromatography has been developed for the quantitative determination of acetylmethadol simultaneously with its two major biotransformation products, noracetylmethadol and dinoracetylmethadol. Noracetylmethadol and dinoracetylmethadol are analyzed following their conversion to the corresponding amides. The amide structure is confirmed by the use of chemical ionization mass spectroscopy and infrared spectroscopy. The method can be used to determine the concentration of acetylmethadol and these compounds in plasma samples from acetylmethadol maintenance subjects. Methadol and normethadol do not attain neasurable plasma levels. Urine contains predominantly noracetylmethadol and dinoracetylmethadol. Evidence was also obtained for the urinary excretion of acetylmethadol, methadol and normethadol. A mean quantity equal to 28% of the administered dose was excreted in the urine of a 48-h dosing interval as acetylmethadol and metabolites.

Biotransformation↗
PubMed1975

Methadone assays in pregnant women and progeny.

Data on the concentration of methadone in maternal plasma and urine of pregnant women on methadone in relationship to levels of amniotic fluid, cord blood, fetal urines, and breast milk are presented. These findings do not demonstrate a simple relationship between methadone levels in the neonate and the intensity of the withdrawal syndrome. The effects of multiple drug abuse and other as yet unknown factors may influence the severity of withdrawal signs in the neonate.

Amniotic Fluid↗
PubMed1975

Disposition of acetylmethadol in relation to pharmacologic action.

The levels of acetylmethadol and its active biotransformation products were quantitated in the plasma and urine of subjects on acetylmethadol maintenance by the use of solvent extraction and gas-liquid chromatography. The time-course of plasma acetylmethadol, noracetylmethadol, and dinoracetylmethadol over 48 hr was determined concurrently with the time-action of pupillary constriction in 8 subjects receiving an average oral maintenance dose of 50 mg. The plasma level of acetylmethadol reached a peak at 4 hr and had nearly disappeared by 24 hr. The mean apparent half-life was 7 hr. The plasma level of noracetylmethadol peaked at 4 to 8 hr and slowly declined over the next 40 hr. The mean apparent half-life of noracetylmethadol was 48 hr. Dinoracetylmethadol plasma levels remained relatively constant throughout the dosing interval. The miotic effect reached a peak at 8 hr and decayed at a rate slower than that of plasma elimination of acetylmethadol but more rapidly than that of noracetylmethadol and dinoracetylmethadol. Substantial variation in the plasma levels of the compounds was observed in subjects after the same doses. The study indicated that the relatively long duration of opiate effects of acetylmethadol results from biotransformation to active and persistent metabolites.

Adult↗
PubMed1975

Stereospecific synthesis of the 6beta-hydroxy metabolites of naltrexone and naloxone.

The narcotic antagonists naltrexone (1a) and naloxone (2a) were stereospecifically reduced to the corresponding 6beta-hydroxy epimers 1b and 2b, respectively, with formamidinesulfinic acid in an aqueous alkaline medium. The reaction products were obtained with no detectable quantity of the 6alpha epimers 1c and 2c. The products 1b and 2b were formed in yields of 88.5 and 40%, respectively, and characterized by spectral methods. Compared to 1a and 2a, the stereospecific reduction products 1b and 2b and their 6alpha epimers 1c and 2c are all significantly less potent as narcotic antagonists in mice. Only 1c and 2c also possess antinociceptive activity.

Animals↗
PubMed1975

Synthesis of alpha-1-noracetylmethadol. A facile N-demethylation of alpha-1-acetylmethadol.

A facile N-demethylation of the narcotic analgesic, alpha-1-acetylmethadol, was accomplished by allowing it to react with mercuric acetate under reflux in dilute acetic acid. The product, alpha-1-noracetylmethadol, was isolated as the hydrochloride in 50% yield. Methadone, when allowed to react with mercuric acetate under the same conditions, did not undergo N-demethylation and was recovered unchanged.

Animals↗
PubMed1975

Narcotic antagonist activity of several metabolites of naloxone and naltrexone tested in morphine dependent mice (38558).

A rabbit liver enzyme system was used to produce the 6beta-OH reduced metabolites of naloxone and naltrexone. GC analysis indicated the presence of some 6alpha-OH metabolite in these samples. The narcotic antagonist activity of these 6beta-OH metabolite samples were compared to naloxone, naltrexone and standard 6alpha-OH naltrexone (EN-2260A) using the jumping response of morphine pellet implanted mice. For the naloxone series, the potencies were: Naloxone greater than EN 2265A greater than 6 beta-OH maloxone. For the naltrexone series: Naltrexone greater than EN 2260A greater than beta-OH naltrexone. The low potency of the reduced metabolites the rapid onset of action of the parent compounds militate against the formation of these metabolites contributing substantially to the overall narcotic antagonist action of the parent compounds.

Animals↗