Hylar L Friedman

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The pharmacokinetics of diazepam (DZ) and its major metabolite desmethyldiazepam (DMDZ) in both plasma and brain after a single 5 mg/kg IP dose of diazepam were studied in rats. Four rats were sacrificed at 5 min, 15 min, 30 min, 1 h, 1.5, 2, 3, 4, 5 and 6 h after the dose. DZ rapidly disappeared from plasma and brain in parallel, with nearly identical(More)
Eleven healthy subjects received single oral doses of placebo, 2 mg diazepam, 5 mg diazepam, and 10 mg diazepam in a randomized four-way crossover study. Plasma diazepam levels, the Digit Symbol Substitution Test (DSST), and fraction of total electroencephalographic (EEG) amplitude falling in the sigma plus beta (13 to 31 Hz) frequency range were determined(More)
Healthy male volunteers (n = 48) aged 18-44 years received a single 10-mg oral dose of diazepam. Plasma diazepam and desmethyldiazepam concentrations were measured at multiple points during the next 11 days. The distribution of peak plasma concentration (mean, 406 ng/ml) was not skewed and did not differ significantly from normal (Guassian). However, the(More)
Ro 15-1788 (flumazepil) is an imidazodiazepine that is able to antagonise most of the behavioural actions of the benzodiazepines, as well as having some intrinsic effects. Acute administration of Ro 15-1788 (10 mg/kg) decreases social interaction between male rats and elevates exploratory head-dipping. After 5 days of pretreatment there was tolerance to the(More)
Concentrations of diazepam (DZ) and desmethyldiazepam (DMDZ) were determined quantitatively in the brain, skeletal muscle, heart, liver, lung, fat, adrenal gland, and kidney in 14 autopsied patients who had been treated with DZ or clorazepate (a DMDZ prodrug) during their hospital course. To facilitate interpatient comparisons, all tissue concentrations(More)
Seven psychotic patients' plasma haloperidol levels, determined with gas-liquid chromatography, fell a mean of 60% when carbamazepine treatment was instituted. Two patients' levels became undetectable, and their symptoms worsened. Haloperidol level monitoring may be required for patients given both haloperidol and carbamazepine.
The comparative pharmacokinetics of alprazolam and lorazepam were evaluated in African Green Monkeys and in healthy male human volunteers. Six monkeys received a single 250 µg/kg oral dose of alprazolam and of lorazepam on two separate occasions. Mean kinetic values for the two drugs, respectively, were: elimination half-life, 5.7 and 1.7 h; oral clearance,(More)
Mestranol, the estrogen component of some oral contraceptive formulations, must be demethylated to its active metabolite, 17 alpha-ethinyl estradiol, to produce estrogenic activity. To investigate the transformation of mestranol to ethinyl estradiol, an in vitro assay was used with human liver microsomes from four different donors. Incubation of a fixed(More)
Nineteen healthy volunteers received a single 0.5-mg oral dose of triazolam on four occasions under the following conditions: (1) triazolam alone; (2) triazolam with cimetidine, 300 mg four times daily; (3) triazolam with propranolol, 40 mg four times daily; (4) triazolam with both cimetidine and propranolol. Triazolam kinetics were determined from multiple(More)