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Biomedical subjects

C W Gorodetzky

Publications and source records attributed to C W Gorodetzky.

At least 19 recordsLinked to original sources
PubMed1986

Diazepam and methadone blood levels following concurrent administration of diazepam and methadone.

Results of a previous study indicated that the opioid effects of methadone were enhanced by the concurrent administration of diazepam in methadone-maintained subjects. To determine whether a pharmacokinetic interaction might account for this methadone-diazepam interaction, the plasma levels of methadone, diazepam and diazepam metabolites were determined in blood samples collected during that study. Five adult male patients on methadone maintenance (50-60 mg/day) were administrated single doses of placebo, diazepam (20 and 40 mg), methadone (100%, 150% and 200% of the maintenance dose), and four diazepam-methadone dose combinations (20 and 40 mg diazepam in combination with 100% and 150% of the maintenance dose). The results showed that the concurrent administration of methadone and diazepam did not significantly change the time-course or areas under the plasma concentration-time curve of methadone, diazepam or N-desmethyl-diazepam compared to the levels following the administration of either drug alone. Thus, plasma drug level analysis does not indicate a pharmacokinetic interaction between diazepam and methadone.

Adult↗
PubMed1986

The pharmacokinetics of pentazocine and tripelennamine.

The pharmacokinetics of single and combined doses of pentazocine HCl (40 and 80 mg) and tripelennamine HCl (50 and 100 mg) were studied in six healthy drug abusers. After intramuscular administration of 40 or 80 mg pentazocine alone, mean peak plasma concentrations at 15 minutes were 102 and 227 ng/ml, respectively, and mean plasma t1/2 values were 4.6 and 5.3 hours, respectively. After intramuscular administration of 50 or 100 mg tripelennamine, mean plasma concentrations at 30 minutes were 105 and 194 ng/ml, respectively, and mean plasma t1/2 values were 2.9 and 4.4 hours, respectively. After concurrent administration of pentazocine with tripelennamine, plasma pentazocine and tripelennamine concentrations at all time points were not significantly different from those when pentazocine or tripelennamine was administered alone. Coadministration of pentazocine and tripelennamine had no effect on the distribution, elimination, and clearance of either pentazocine or tripelennamine. In conclusion, there did not appear to be a clinically significant metabolic interaction between pentazocine and tripelennamine.

Adult↗
PubMed1985

63Ni electron-capture gas chromatographic assay for buprenorphine and metabolites in human urine and feces.

A 63Ni electron-capture gas chromatographic assay is described for buprenorphine, a potent narcotic agonist--antagonist. In addition, the assay is useful for the measurement of the metabolite norbuprenorphine and demethoxybuprenorphine, a rearrangement product resulting when buprenorphine is exposed to acid and heat. An extraction procedure was developed which optimized recovery of buprenorphine from biological samples and produced minimal background interferences and emulsion problems. Extract residues were derivatized with pentafluoropropionic anhydride and assayed by gas chromatography. Samples were analyzed with and without enzyme hydrolysis, thus providing a selective and sensitive assay for both free and conjugated buprenorphine, norbuprenorphine and demethoxybuprenorphine. The lower limits of detection following extraction of a 1-ml sample were ca. 10 ng/ml for buprenorphine and demethoxybuprenorphine and 5 ng/ml for norbuprenorphine. Application of the assay to human samples following a 40-mg oral dose of buprenorphine produced no evidence for the presence of demethoxybuprenorphine in urine or feces. Norbuprenorphine (free and conjugated) was present in urinary and fecal samples; buprenorphine (free and conjugated) was found in high amounts only in feces and in trace amounts in urine as conjugated buprenorphine. The urinary and fecal excretion pattern observed for a human subject following oral dosing of buprenorphine suggests enterohepatic circulation of buprenorphine.

Adult↗
PubMed1979

Isolation and identification of morphine n-oxide alpha- and beta-dihydromorphines, beta- or gamma-isomorphine, and hydroxylated morphine as morphine metabolites in several mammalian species.

New morphine metabolites in the urine of guinea pigs, rats, rabbits, cats, monkeys, and humans were isolated with column chromatography, solvent extraction, and TLC and identified with TLC, GLC, and GLC-mass spectrometry. In addition to the known morphine metabolites, morphine N-oxide was isolated from the urine of guinea pigs, and alpha- and beta-dihydromorphines were isolated or detected in the urine of guinea pigs, rats, and rabbits. Monohydroxymorphine was identified tentatively in the urine of guinea pigs, rats, rabbits, and cats. Dihydroxymorphine was identified tentatively in the urine of guinea pigs, rats, and possibly, rabbits. Finally, beta- or gamma-isomorphine was identified tentatively in the urine of guinea pigs. The newly described morphine metabolites may be involved in some long lasting pharmacological effects of morphine.

Animals↗
PubMed1979

Comparative metabolism of codeine in man, rat, dog, guinea-pig and rabbit: identification of four new metabolites.

The metabolism and excretion of codeine and its metabolites in untreated urine of man, rat, dog, guinea-pig and rabbit have been examined. Metabolites were identified by gas chromatography mass spectrometry operated in the chemical ionization mode (methane). Concentrations of codeine and metabolites were measured by selected ion monitoring. Both codeine and norcodeine were detected in the urine of all species but a new metabolite, hydrocodone, was found only in the urine from man, guinea-pig and dog. Additional metabolites (presumably resulting from the metabolism of hydrocodone) were also detected in man and guinea-pig. Overall recoveries of drug and metabolites from untreated urine were low for all species.

Adult↗
PubMed1978

Metabolism and excretion of normorphine in dogs.

Normorphine metabolism was studied in dogs given 20 mg of normorphine hydrochloride/kg sc. Free and (onjugated normorphine excreted in the urine over 144 hr represented 32 and 32%, respectively, of the administered dose. Eighty percent of the urinary excretion of the drug occurred within 9 hr. One percent of the administered dose was excreted as free normorphine in the feces. The urine was chromatographed on a column. Evaporation of the washing and methanolic effluent yielded a residue, which was purified by crystallization from aqueous methanol. Results of UV and IR studies, elemental analysis, and determination of normorphine and glucuronic acid content established the identity of this metabolite as normorphine 3-glucuronide. Dihydronormorphine and dehydronormorphine were detected with GLC-mass spectrometry as minor metabolites.

Animals↗
PubMed1978

Possible effects of normetabolites on the subjective and reinforcing characteristics of opioids in animals and man.

When an opioid capable of forming active metabolites is administered, the total pharmacology is the result of interactions of the opioid and such metabolites, especially normetabolites. Normetabolites may affect the morphine-like characteristics of certain opioids and thus influence their reinforcement in animals and man. Most opioids, when administered in single doses, are positively reinforcing in addicts. Oral administration, as compared with parenteral, facilitates the formation of normetabolites. When chronically administered, many opioids, including acetylmethadol, meperidine, morphine, codeine, propoxyphene, and levorphanol, show evidence of a longer half-life for their normetabolites. Normetabolites may have aversive characteristics and thus impair positive reinforcement of the parent drug in animals and man. For example, addicts do not like chronic oral morphine or chronic oral codeine. Conversely, methadone, the normetabolites of which are inactive, is well accepted during chronic oral administration. Drugs which inhibit N-demethylation will increase the agonist potency of opioids having inactive normetabolites (e.g., methadone) but will decrease the agonist potency of opioids having more potent normetabolites than the parent (e.g., acetylmethadol). The divergent responses of addicts to single doses of opiates as compared with chronic doses indicate that chronic addiction tests in man are needed befored relative abuse liability can be predicted.

Animals↗
PubMed1978

The identification and measurement of two new metabolites of naltrexone in human urine.

Two metabolites of naltrexone were identified in human and rat urine following drug administration. The metabolites, 2-hydroxy-3-0-methylnatrexone and 2-hydroxy-3-0-methyl-6 beta-naltrexol, were identified by comparison of their respective gas chromatographic retention times and methane chemical ionization spectral patterns with authentic standards. The standards were obtained by chemical synthesis from naltrexone. Urinary excretion of the two metabolites was measured by single ion recording of the pseudomolecular ions of the metabolites and an internal standard. Excretion data was collected from 5 human subjects over a period of 5 days following a single dose of naltrexone. The metabolites, 2-hydroxy-3-0-methylnatrexone and 2-hydroxy-3-0-methyl-6 beta-natrexol were found to account for an average (+/- standard error) of 0.45 +/- 0.08% and 4.6 +/- 2.1% of the administered dose, respectively. An unusually long half-life of elimination of the latter metabolite (mean of 20.2 +/- 1.8 hr) was observed. Acid-hydrolysis of the samples failed to produce a significant increase of either metabolite indicating that the major protion of these metabolites is excreted in the free form.

Animals↗
PubMed1977

Identification of diacetylmorphine metabolites in humans.

With the techniques of column chromatography, TLC, and GLC, morphine, 6-acetylmorphine, normorphine, morphine 3-glucuronide, 6-acetylmorphine 3-glucuronide, and normorphine glucuronide were identified as metabolites of diacetylmorphine (heroin) in the urine of humans administered 10 mg iv/70 kg body weight.

Adult↗
PubMed1977

Isolation and identification of morphine 3- and 6-glucuronides, morphine 3,6-diglucuronide, morphine 3-ethereal sulfate, normorphine, and normorphine 6-glucuronide as morphine metabolites in humans.

Morphine metabolites were isolated with column chromatography on a resin and neutral aluminum oxide and TLC from the urine of morphine-dependent subjects maintained on morphine sulfate at a dose of 240 mg/day. These metabolites were characterized as morphine 3-glucuronide, morphine 6-glucuronide, morphine 3,6-diglucuronide, morphine 3-ethereal sulfate, normorphine, normorphine 6-glucuronide, and, possibly, normorphine 3-glucuronide by free phenol and glucuronide tests, enzymatic hydrolysis, GLC, TLC, UV spectroscopy, and GLC--mass spectrometry.

Adult↗
PubMed1977

Urinary excretion of hydromorphone and metabolites in humans, rats, dogs, guinea pigs, and rabbits.

Hydromorphone was administered as a single dose to humans, rats, dogs, guinea pigs, and rabbits, and timed urinary collections were made. GLC-mass spectrometric and GLC analyses of the samples revealed the presence of the parent compound and both 6-hydroxy epimers as metabolites in the urine of all species. Free or conjugated parent drug predominated, while levels of free or conjugated 6beta-hydroxy metabolite were higher than or equal to those of the 6alpha-form. The time courses of excretion of drug and metabolites were similar for all species, with the major portion being excreted in the first 24 hr. Generally, free and conjugated drug were undetectable in human urine after 8 and 48 hr, respectively.

Adult↗
PubMed1976

Urinary excretion of heroin and its metabolites in man.

The purpose of this study was to investigate the kinetics of urinary excretion of heroin and its metabolites in human subjects. Heroin and its metabolites were determined with gas-liquid chromatography. Two studies were conducted, each using 10 subjects. After i.v. administration of heroin HC1, 10 mg/70 kg, urine was collected every 8 hours and ad libitum for 1 week in the first study and every 2 hours in the first 8 hours and then at less frequent intervals for 24 hours in the second study. Heroin, 6-acetylmorphine, morphine, the sum of conjugates (morphine plus 6-acetylmorphine) and total normorphine were determined in the first 24-hour urine and accounted for 0.5, 1.5, 7.2, 52 and 4%, respectively, of the administered dose. Conjugated morphine could be detected in the urine 96 hours after drug administration. Eighty-eight percent of the free morphine and 84% of the total morphine found in the urine were excreted in the first 8 hours. The half-lives of urinary excretion of free morphine, 6-acetylmorphine, the sum of conjugates (morphine plus 6-acetylmorphine) and total normorphine were 1.28, 1.31, 2.76 and 2.72 hours, respectively. It was concluded that heroin in the body was rapidly metabolized and its metabolites were rapidly excreted in the urine.

Adult↗
PubMed1975

Etrophine in man. II. Detectability in urine by common screening methods.

A single highly euphorogenic dose of etorphine, 100 mug, was administered subcutaneously to 7 nontolerant subjects, and all urine samples were collected for 1 day prior to and 3 days following drug administration. Samples were analyzed for the presence of opiates by radioimmunoassay (Abuscreen) and homogeneous enzyme immunoassay (EMIT), with cutoffs for "ositives" of 40 and 500 ng/ml, respectively. Samples were analyzed for etorphine by thin-layer chromatography (TLC) with iodoplatinate preceded by XAD-2 resin extraction (sensitivity = 0.2 mug etorphine/ml of urine) and by gas-liquid chromatography (GLC) preceded by organic solvent extraction and trimethylsilyl derivatization (sensitivity = 0.1 mug etorphine/ml of urine). The last pre-drug and first two post-drug samples were also analyzed after acid hydrolysis by TLC and after glucuronidase hydrolysis by TLC and GLC. No sample gave a "positive" opiate result in either immunoassay, and no etorphine was detected in the TLC and GLC analyses of any urine sample. Thus, it is unlikely that the abuse of etorphine could be diagnosed by urinalysis using the common screening methods of radioimmunoassay, EMIT, TLC preceded by XAD-2 resin extraction, or GLC preceded by organic solvent extraction and trimethylsilyl derivatization.

Adult↗
PubMed1975

Biosynthesis, isolation, and identification of 6-beta-hydroxynaltrexone, a major human metabolite of naltrexone.

Chemical reduction of naltrexone is described in an attempt to synthesize 6-beta-hydroxynaltrexone. Only the epimer, 6-alpha-hydroxynaltrexone, was produced. Pilot metabolic studies on naltrexone in the dog, rat, and guinea pig were made to determine which animal produced the greatest amount of 6-beta-hydroxynaltrexone. The guinea pig was selected and used to produce the metabolite. Isolation and purification methods are described, and spectral data are presented for structural confirmation of the metabolite.

Animals↗