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Biomedical subjects

J Edelson

Publications and source records attributed to J Edelson.

At least 19 recordsLinked to original sources

A comparison of cognitive-behavioral and hypnotic treatments of chronic pain.

Twenty-seven chronic pain patients were assigned to one of three treatment groups: hypnosis, cognitive-behavioral, and an attention control. Hypnosis and cognitive-behavioral treatments were identical with the exception of the hypnotic induction. Scores on the McGill Pain Questionnaire (MPQ) and the Activity Log (Fordyce, 1976) were collected at pretreatment, posttreatment, and follow-up intervals. Analyses of changes showed significant increases in activity and decreases in pain intensity for the cognitive-behavioral treatment. Changes for the hypnosis treatment were noted only on the MPQ. Changes for both groups were sustained on the 1-month follow-up. Results of ANCOVAs showed that the cognitive-behavioral treatment resulted in significantly lower pain rating scores than those in the control treatment, but no significant differences were observed between the behavior and hypnosis groups. Findings support the superiority of the cognitive-behavioral treatment on behavior measures and equivalence to hypnosis on subjective measures.

Adult

Effect of the acetylator phenotype on amrinone pharmacokinetics.

Ten healthy male subjects were phenotyped with isoniazid for their acetylator status and then received intravenous amrinone at a dose of 75 mg during a period of 10 minutes. Blood samples were drawn at specified times during a 24-hour period after dosing. Plasma concentrations of amrinone were determined by a specific HPLC method. The plasma concentration data were fitted to a biexponential model by nonlinear regression. The mean apparent first-order elimination t1/2 for amrinone in the slow acetylators was 4.4 hours, whereas it was 2.0 hours in the fast acetylators (P less than 0.05). There was little difference in the volume of distribution at steady state. Clearance was lower in the slow acetylators, 16.6 L/hr, than in the fast acetylators, 37.2 L/hr (P less than 0.05). The AUC was higher for the slow acetylators, 4.96 micrograms X hr X ml-1, than for the fast acetylators, 2.20 micrograms X hr X ml-1 (P less than 0.01). Concentrations of amrinone and its N-acetyl metabolite in the urine from each volunteer were determined. The ratio of N-acetylamrinone to amrinone was calculated and, as expected, the fast acetylators had a higher ratio than did the slow acetylators (P less than 0.01).

Acetylation

Pharmacokinetics of the bipyridines amrinone and milrinone.

The pharmacokinetics of milrinone were studied in sequential ascending doses in New York Heart Association Class III and IV patients receiving oral and intravenous medication. The parameters determined after parenteral administration were estimated by fitting the plasma concentration data to an open two-compartment body model. After oral medication, regression-independent parameters were determined. After either oral or parenteral administration of milrinone, plasma levels were dose dependent and the drug had an apparent first-order terminal elimination half-life of approximately 2 hr. The apparent volume of distribution was approximately 400 to 500 ml/kg, and total body clearance was approximately 130 ml/kg/hr. These values obtained in patients receiving milrinone were compared with those obtained for milrinone in volunteers, as well as those noted with the other inotropic bipyridine, amrinone. Milrinone's elimination from the blood stream patients was slower that that in normal healthy subjects and faster than amrinone's elimination in patients with congestive heart failure. Milrinone's pharmacokinetic parameters in these patients were unchanged after approximately 30 days of continuous oral medication.

Administration, Oral

Determination of fezolamine and its desmethyl metabolite in human plasma and urine by high-performance liquid chromatography. Intravenous pharmacokinetics in the beagle hound.

Sensitive and selective high-performance liquid chromatographic methods for the quantitation of the experimental antidepressant fezolamine and its desmethyl metabolite in plasma and urine have been developed. Both assays are linear between 0 and 500 ng/ml in both plasma and urine and have calculated minimum quantifiable levels of less than 10 ng/ml. Statistical evaluation of analytical parameters under single-blind conditions demonstrated an overall precision within +/- 4% of nominal for both compounds in either biological medium. The overall accuracies of the assays were within +/- 5% of nominal values in urine and +/- 10% of nominal values in plasma. Following intravenous administration of fezolamine fumarate to beagle hounds, a biexponential decline in drug plasma levels was observed with the first phase having a half-life of about 11 min and the second phase about 2.6 h. Peak plasma levels of the metabolite were observed at 2 h. Recovery of the parent drug in urine was less than 5% of the administered dose and less than 1% for the desmethyl metabolite.

Animals

Relative bioavailability and pharmacokinetics: a combination of pentazocine and acetaminophen.

The relative bioavailability and pharmacokinetics of a combination product containing pentazocine and acetaminophen were studied in 20 healthy human males. Each subject, in a single-dose three-way crossover design, received two different preparations containing 50 mg of pentazocine (as base) and 1300 mg of acetaminophen either as capsule-shaped tablets or as a solution. Plasma concentrations of pentazocine and acetaminophen were determined from 0.25 to 12 h following oral administration. The plasma data for both compounds in the tablet formulation were described by an open one-compartment body model with first-order absorption. The average (+/- SD) bioavailability of the tablet relative to that of the solution was 85.0 +/- 31.1 and 88.6 +/- 13.1% for pentazocine and acetaminophen, respectively. The apparent first-order regression-dependent elimination rate constants for pentazocine from the tablet and solution preparations were 0.19 +/- 0.08 and 0.20 +/- 0.06 h-1, respectively, while the rate constants for acetaminophen were 0.26 +/- 0.03 and 0.25 +/- 0.03 h-1 for the tablet and solution preparations, respectively. These rate constants correspond to terminal elimination half-lives of approximately 3.6 h for pentazocine and approximately 2.7 h for acetaminophen.

Acetaminophen

Pharmacokinetics of iohexol, a new nonionic radiocontrast agent, in humans.

Sixteen healthy men received iohexol intravenously at a concentration of 346 mg of iodine/mL. Doses of 500, 750, 1000, and 1500 mg of iodine/kg of body weight were administered to four volunteers each. Neither clearance nor percent of dose excreted in the urine showed any significant correlation with size of the dose. The overall mean (+/- SD) renal and total body clearances were 120 +/- 18.6 and 131 +/- 18.6 mL/min, respectively. The overall mean apparent volume of distribution was 165 (+/- 30.7) mL/kg. Urine contained 92.3 +/- 4.4% of the dose. Most of the drug (89.9%) was excreted within the first 12 h. An open three-compartment body model gave the best fit to the experimental data. The mean apparent first-order terminal elimination (gamma-phase) half-life was 12.6 h.

Adolescent

Oral and intravenous pharmacokinetics of milrinone in human volunteers.

Thirty-nine healthy men received milrinone either orally or intravenously in two separate double-blind, placebo-controlled studies. The mean bioavailability, based on the area under the plasma concentration versus time curves, was 0.92. The plasma data for those subjects in the intravenous study were described by an open two-compartment model with a mean (+/- SD) apparent first-order terminal elimination rate constant (beta) of 0.86 (+/- 0.23) h-1, which corresponds to a half-life of 0.8 h. In the intravenous study, the renal clearance and total body clearance were 21.1 and 25.9 L/h, respectively. The corresponding values in the oral study were 23.8 and 29.7 L/h. Between 79.9 and 84.5% of the total doses were recovered in the urine samples taken at 0-24 h.

Administration, Oral

Correlation of the hemodynamic and pharmacokinetic profile of intravenous milrinone in the anesthetized dog.

The relationship between the hemodynamic effects of milrinone and its plasma concentration was studied in the anesthetized instrumented dog. Milrinone was administered intravenously either as a single bolus of 10, 30 or 100 micrograms/kg or infused at a rate of 10 micrograms/kg/min. The changes in drug plasma concentration and cardiovascular parameters were determined simultaneously during the course of drug action. The intravenous bolus injections of milrinone caused dose-dependent increases in its maximum plasma concentration that resulted in concomitant increases in both cardiac contractile force and heart rate with simultaneous decreases in systolic and diastolic blood pressure. The intravenous infusion of milrinone caused parallel increases in both drug plasma concentration and cardiac contractile force; following termination of the milrinone infusion, there was a gradual decline in both its plasma concentration and in its inotropic activity, with a similar time course for these two parameters. A positive correlation (r = 0.78; p less than 0.008) was obtained between milrinone plasma concentration and its inotropic effect.

Anesthesia

Evaluation of a new bipyridine inotropic agent--milrinone--in patients with severe congestive heart failure.

Milrinone, a derivative of amrinone, has nearly 20 times the inotropic potency of the parent compound and does not cause fever or thrombocytopenia in normal volunteers or in animals sensitive to amrinone. In 20 patients with severe congestive heart failure, intravenous milrinone resulted in significant decreases in left ventricular end-diastolic pressure (from 27 +/- 2 to 18 +/- 2 mm Hg), pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance, as well as a slight reduction in mean arterial pressure. Significant increases occurred in cardiac index (from 1.9 +/- 0.1 to 2.9 +/- 0.2 liters per minute per square meter) and the peak positive first derivative of left ventricular pressure, with a slight increase in heart rate. Hemodynamic improvement was sustained during a 24-hour continuous infusion. Nineteen of the 20 patients subsequently received oral milrinone (29 +/- 2 mg per day) for up to 11 months (mean, 6.0 +/- 0.8), with sustained improvement in symptoms of heart failure. In 10 patients receiving long-term oral milrinone (greater than or equal to 6 months) radionuclide ventriculography showed continued responsiveness, with a 27 per cent increase in left ventricular ejection fraction after 7.5 mg of the drug. Four patients died after a mean of 4.8 months of therapy, and three patients with severe underlying coronary-artery disease and angina pectoris required additional antianginal therapy. No patient had fever, thrombocytopenia, gastrointestinal intolerance, or aggravation of ventricular ectopy. We conclude that milrinone shows promise for the longterm treatment of congestive heart failure.

Administration, Oral

Oral bioavailability and intravenous pharmacokinetics of amrinone in humans.

Fourteen healthy males received two 75-mg doses of amrinone as a single capsule and as an intravenous solution in a single-dose crossover study. The mean (+/-SD) bioavailability, based on the area under the plasma concentration versus time curves, was 0.93 +/- 0.12. The plasma data for these subjects during the intravenous phase was described by an open two-compartment body model with a mean (+/-SD) apparent first-order terminal elimination rate constant, beta, of 0.19 +/- 0.06 hr-1, which corresponds to a half-life of 3.6 hr.

Administration, Oral

Dose proportionality of amrinone.

Amrinone was given to 18 healthy subjects in doses of 75, 150, and 225 mg in a randomized crossover design. Plasma levels were shown to rise in proportion to dose. The mean plasma AUC, extrapolated to infinite time, was determined for each dose level; the values obtained were 4, 8.18, and 12.35 micrograms . hr/ml for the 75-, 150-, and 225-mg doses. Mean maximum observed plasma concentrations were 1.03, 1.74, and 2.58 micrograms/ml. At higher doses the extrapolated AUC is more variable, but it is linear over the range of 0.73 to 3.81 mg/kg. The apparent first-order terminal elimination rate is not dose dependent and corresponds to a t1/2 of 3.85 hr.

Adult

Determination of azarole plus its reduction product by HPLC.

An analytical methodology for the assay of azarole plus its reduced product in plasma was developed. The method consists of oxidation of the sample with potassium ferrocyanide, extraction, and subsequent analysis by high performance liquid chromatography. Assays of prepared plasma samples demonstrated an overall precision of +/- 6.2%; accuracy ranged from -9.1% low to 5.1% high, based on mean values at several concentrations. Analysis of variance for the effects of concentration, time, and the interactive term concentration X time were all insignificant.

Chromatography, High Pressure Liquid

Pharmacokinetics of rosoxacin in human volunteers.

Reversed-phase liquid chromatography was used to determine plasma rosoxacin concentrations in normal, healthy males, each of whom received one 300 mg capsule of rosoxacin. The plasma data for each subject were described by an open one-compartment body model with first-order absorption, and the pharmacokinetic parameters were determined. The mean (+/- SE) apparent first-order terminal elimination rate constant was 0.203 +/- 0.015 hr-1 (N = 16), the mean apparent volume of distribution was 0.644 +/- 0.050 liters/kg, and the mean apparent plasma clearance was 2.08 +/- 0.15 ml/min/kg.

4-Quinolones