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Biomedical subjects

M Perez-Reyes

Publications and source records attributed to M Perez-Reyes.

At least 55 records · Page 3Linked to original sources

Intravenous injection in man of 9 -tetrahydrocannabinol and 11-OH- 9 -tetrahydrocannabinol.

A microsuspension of Delta(9)-tetrahydrocannabinol and of its metabolic derivative 11-OH-Delta(9)-tetrahydrocannabinol has been prepared with 25 percent human serum albumin as the vehicle. Intravenous infusion of this preparation to humans indicates that both tetrahydrocannabinols are equally potent in producing the typical marihuana-like pschological and physiological effects.

Adult↗

The metabolism of delta 9-tetrahydrocannabinol and related cannabinoids in man.

The metabolism of delta 9-tetrahydrocannabinol (THC) and related cannabinoids in man has been studied in detail utilizing intravenous, oral, and smoking routes of administration. The general pattern of metabolism was the same in all studies involving THC and related cannabinoids. Microsomal hydroxylation allylic to the delta 9-THC double bond occurs, the major product resulting in formation of an 11-CH2OH moiety; minor hydroxylation occurs on the C-8 carbon. Nonmicrosomal oxidation of the resultant 11-OH-delta 9-THC to 11-nor-delta 9-THC-9-carboxylic acid and to other more polar acids generates the major terminal metabolic products. After oral administration, approximately equal quantities of THC and its highly active 11-hydroxymetabolite were formed, whereas the latter metabolite is a minor constituent after administration by intravenous or smoking routes. Initial pharmacokinetic analyses of the data show that the mean terminal-phase (beta-phase) plasma half-life after intravenous administration of THC was about 30 hours; after oral administration, it was 23 hours. No significant statistical difference was noted between men and women as to metabolic routes or plasma terminal-phase half-lives.

Administration, Oral↗

The clinical pharmacology and dynamics of marihuana cigarette smoking.

We have studied the dynamics of marihuana smoking, the plasma concentration of delta 9-tetrahydrocannabinol (THC), and the pharmacologic effects produced by the sequential smoking of two 1% marihuana cigarettes at a 2-hour interval. Three males and three females, experienced marihuana smokers, participated in the study. The results indicate that each subject smoked his or her two cigarettes at a similar rate. The THC plasma concentrations produced by the smoking of the second cigarette were slightly lower than those produced by the first cigarette. The levels of the psychologic "high" caused by the two cigarettes were similar. However, the first cigarette accelerated the heart twice as much as the second cigarette. Between males and females there were marked differences in the rate at which the cigarettes were smoked. In particular, males took more puffs, took them more often, and consumed the cigarettes more rapidly than females. The plasma concentrations of THC, the self-reported psychologic effects, and the heart rate acceleration produced by the smoking of the two cigarettes were identical between the sexes.

Cannabis↗

Cannabinoid concentrations in plasma after passive inhalation of marijuana smoke.

delta-9-tetrahydrocannabinol (THC) and its metabolite, 9-carboxy-THC, were detected in the plasma of a subject during a one-hour passive exposure to the smoke from four marijuana cigarettes containing a total of 104.8 mg of THC. Plasma concentrations of THC were determined by RIA and reached an apparent steady-state concentration of 2.2 ng/mL after 20 minutes of exposure. The presence of THC was confirmed by GC/MS analysis. Results from the two analyses exhibited excellent correlation (r = 0.990), although the concentrations determined by GC/MS were higher than those determined by RIA. Concentrations of 9-carboxy-THC were also determined by GC/MS, and remained consistently below the GC/MS determined concentrations of THC. By administering an infusion of THC, the dose that was inhaled and absorbed during the passive exposure was estimated to be 3.2 micrograms/min.

Adult↗

MR appearance of umbilical endometriosis.

OBJECTIVE: We describe the MR appearance of endometriosis involving the umbilicus in two patients. One patient had a history of laparoscopy performed through the umbilicus; the other had an umbilical hernia. MATERIALS AND METHODS: MR imaging was performed using both a body coil and a spine coil (with the patient lying prone on the spine coil). The lesions were surgically removed and their MR appearance was correlated with the results of histologic analysis. RESULTS: The lesions were well delineated on MRI and showed evidence of prior hemorrhage consistent with endometriosis. Both lesions were shown to be endometriosis at surgical pathology. CONCLUSION: MR imaging was useful for delineating the size and location of the lesions and excluding intraabdominal extension.

Adult↗

Pharmacokinetics of oral methamphetamine and effects of repeated daily dosing in humans.

The pharmacokinetics of orally administered S-(+)-methamphetamine-d3 were investigated in human male volunteers before and after a 13-day course of a slow release form of S-methamphetamine hydrochloride. A one-compartment pharmacokinetic model incorporating a lag time fits the data best. The average elimination half-life was 10.1 hr (range of 6.4-15.1 hr). There were no statistically significant differences in pharmacokinetic parameters when a low dose (0.125 mg/kg) was given before and after the 13-day oral regimen. When a higher challenge dose (0.250 mg/kg) was used, the maximum plasma concentration of methamphetamine-d3 was slightly but significantly greater when the test dose was given at the end of the oral dosing period than when it was given at the beginning. Although minor differences in pharmacokinetics occur after subchronic treatment with low doses of methamphetamine, their result would be to increase plasma concentration of the drug. Therefore, development of pharmacodynamic tolerance to methamphetamine could not be explained on the grounds of a change in pharmacokinetics.

Administration, Oral↗

Cocaine disposition in humans after intravenous injection, nasal insufflation (snorting), or smoking.

The disposition of radiolabeled cocaine in humans has been studied after three routes of administration: iv injection, nasal insufflation (ni, snorting), and smoke inhalation (si). Metabolism, followed by urinary excretion of metabolites, proved to be the major route of elimination in all cases. Hydrolytic products (benzoylecgonine, ecgonine methyl ester) were the major excretion products. Benzoyl ecgonine was generally most prevalent, but after smoking two subjects excreted larger amounts of ecgonine methyl ester and the ratio of the two compounds averaged lower in subjects who smoked cocaine. Low binding of cocaine to plasma proteins was observed and blood to plasma ratios were essentially unity. The volume of distribution of cocaine is low (2.70 liter/kg for V beta). Absorption of smoked cocaine was rapid (half-time of 1.1 min). Absorption after ni was slower (half-time of 11.7 min). After iv injection, a rapid distribution phase was observed (half-life of 11 min) and the elimination half-life was 78 min. In 16 subjects divided into three groups based on routes, the half-life based on the average rate constant was 69 min. Bioavailability was good after ni (80%). Undecomposed cocaine from si was well absorbed, but observed bioavailability was diminished by degradation from heating.

Administration, Intranasal↗

Metabolism and disposition of naltrexone in man after oral and intravenous administration.

The metabolism and elimination of [15, 16,-3H2]naltrexone was studied in man after oral and intravenous administration. The same metabolites, although in varying proportions, were observed in both cases; conjugated naltrexone and conjugated and unconjugated 6 beta-naltrexol were the major metabolites observed in plasma, urine, and feces. 2-Hydroxy-3-O-methyl-6 beta-naltrexol was found in minor quantities. Naltrexone was almost completely absorbed after oral administration. After oral and intravenous administration of naltrexone, about 60% of the dose was recovered in the urine in 48 and 72 hr, respectively. The route of administration did not significantly affect urinary clearance values obtained for unconjugated or conjugated naltrexone and 6 beta-naltrexol. The route of administration significantly affected terminal plasma half-life values obtained for unconjugated naltrexone (2.7 hr, iv; 8.9 hr, oral), but had little effect on comparable values obtained for total drug, conjugated naltrexone, and unconjugated and conjugated 6 beta-naltrexol. Combined gas chromatography-mass spectrometry was used to validate the presence of naltrexone, 6 beta-naltrexol, and 2-hydroxy-3-O-methyl-6 beta-naltrexol in urine.

Administration, Oral↗