Healthcare reform will affect cancer care continuum.
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Biomedical subjects
Publications and source records attributed to M Bliss.
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The use of fiberoptic light in association with a movable stereoscope and gloveless chamber has greatly enhanced our ability to detect and manipulate minute bacterial colonies on plates used for primary cultures of anaerobes as early as 24 hours postinoculation. Additional benefits resulting from this association are ease in screening anaerobic plates, increased work space within the chamber, and an additional light source that can be used independent of the stereoscope.
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Amiodarone has been reported to increase phenytoin levels. This study was designed to evaluate the pharmacokinetic basis of this interaction at steady-state. Pharmacokinetic parameters for phenytoin were determined after 14 days of oral phenytoin, 2 to 4 mg/kg/day, before and after oral amiodarone, 200 mg daily for 6 weeks in 7 healthy male subjects. During amiodarone therapy, area under the serum concentration time curve for phenytoin was increased from 208 +/- 82.8 (mean +/- standard deviation) to 292 +/- 108 mg.hr/liter (p = 0.015). Both the maximum and 24-hour phenytoin concentrations were increased from 10.75 +/- 3.75 and 6.67 +/- 3.51 micrograms/ml to 14.26 +/- 3.97 (p = 0.016) and 10.27 +/- 4.67 micrograms/ml (p = 0.012), respectively, during concomitant amiodarone treatment. Amiodarone caused a decrease in the oral clearance of phenytoin from 1.29 +/- 0.30 to 0.93 +/- 0.25 liters/hr (p = 0.002). These results were due to a reduction in phenytoin metabolism by amiodarone as evidenced by a decrease in the urinary excretion of the principal metabolite of phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin, 149 +/- 39.7 to 99.3 +/- 40.0 mg (p = 0.041) and no change in the unbound fraction of the total phenytoin concentration expressed as a percentage, 10.3 +/- 2.7 versus 10.7 +/- 2.1% (p = 0.28) during coadministration of amiodarone. The alterations in phenytoin pharmacokinetics suggest that steady-state doses of phenytoin of 2 to 4 mg/kg/day should be reduced at least 25% when amiodarone is concurrently administered. All dosage reductions should be guided by clinical and therapeutic drug monitoring.
To determine the mechanism of the amiodarone-phenytoin interaction, seven healthy male subjects were given intravenous phenytoin, 5 mg/kg, before (phase I) and after (phase II) 3 weeks of oral amiodarone, 200 mg/day. Serum AUC increased from 245 +/- 37.6 to 342 +/- 87.3 mg.hr/L (p = 0.007); area under the first moment curve increased from 5666 +/- 1003 to 11,632 +/- 4198 mg.hr2/L (p = 0.008); the time-averaged total body clearance decreased from 1.57 +/- 0.3 to 1.17 +/- 0.33 L/hr (p = 0.0004); and the apparent elimination half-life increased from 16.1 +/- 1.32 to 22.6 +/- 3.8 hours (p = 0.001) for phenytoin during phase II. The volume of distribution at steady state and the unbound fraction for phenytoin remained unchanged. However, the formation of p-hydroxyphenytoin as a function of serum phenytoin concentration decreased during phase II. These findings suggest that amiodarone inhibits phenytoin metabolism. These observations also suggest that phenytoin doses will need to be reduced when coadministered with amiodarone. The magnitude of this reduction is difficult to predict because of the saturable pharmacokinetics of phenytoin, and therapeutic monitoring is recommended if amiodarone is added to the phenytoin regimen.
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A monoclonal antibody to phencyclidine was developed, produced in mouse ascites fluid, and purified. The purification used only preparative-scale isoelectric focusing in the Rotofor and dialysis. In 4 h, 25% (4 mg) of the antibody from 10 ml of ascites fluid was purified to homogeneity while 63% of the total antibody was recovered.
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The pharmacokinetics of digoxin were studied before and after a 2 week course of diltiazem, 30 mg four times daily, in 7 healthy volunteers. Each subject received an IV dose of digoxin before starting diltiazem and again on day 15 of the study. Diltiazem was continued until all sera and urine were collected. During the control and diltiazem phases, respectively, the terminal elimination rate constants were 0.0231 +/- 0.007 h-1 and 0.0254 +/- 0.007 h-1, the volumes of distribution were 10.5 +/- 3.95 l/kg and 10.2 +/- 3.26 l/kg, and the total body clearances were 3.72 +/- 0.78 ml X min-1 X kg-1 and 4.09 +/- 0.94 ml X min-1 X kg-1. None of these pharmacokinetic parameters of digoxin were significantly different before or during diltiazem administration. Overall, there does not appear to be an interaction between digoxin and diltiazem.
Cimetidine absorption after a single 300 mg oral dose was evaluated in six normal subjects in the absence or presence of sucralfate. Sucralfate was ingested four times a day for 2 days prior to and for two additional doses on the day of cimetidine ingestion. Sucralfate coadministration had no statistically significant influence on the rate or extent of cimetidine absorption.
Cefamandole disposition kinetics were examined in six male subjects with renal impairment who were undergoing continuous ambulatory peritoneal dialysis. Creatinine clearance values ranged from less than 1 to 11 ml/min. Cefamandole was given as a 1-g intravenous dose infused over 30 min. Cefamandole concentrations were determined in serum, urine, and dialysis fluid by a high-performance liquid chromatographic method. The following average parameter values were obtained (range): half-life, 6.1 h (4.6 to 9.7); systemic clearance, 21.9 ml/min (8.4 to 35.5); renal clearance, 11.5 ml/min (0.03 to 22.3); dialysis clearance, 0.92 ml/min (0.7 to 1.3); nonrenal clearance, 12.2 ml/min (2.9 to 27.0); volume of distribution, 0.18 liter/kg (0.09 to 0.25); steady-state volume of distribution, 0.17 liter/kg (0.09 to 0.24). Approximately 5% of the dose was dialyzed (range, 2.8 to 8.3), indicating that there is no need to supplement a dosing regimen of cefamandole due to loss by dialysis. There was a positive correlation between creatinine clearance and the terminal elimination rate constant of cefamandole (r2 = 0.41) and cefamandole renal clearance (r2 = 0.83).
The stability of amiodarone hydrochloride in intravenous admixtures was studied. Amiodarone hydrochloride 900 mg was mixed with 500 mL of either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers; identical solutions were also mixed with either potassium chloride 20 meq, lidocaine hydrochloride 2000 mg, quinidine gluconate 500 mg, procainamide hydrochloride 2000 mg, verapamil hydrochloride 25 mg, or furosemide 100 mg. All admixtures were prepared in triplicate and stored for 24 hours at 24 degrees C. Amiodarone concentrations were determined using a stability-indicating high-performance liquid chromatographic assay immediately after admixture and at intervals during storage. Each solution was visually inspected and tested for pH. Amiodarone concentrations decreased less than 10% in all admixtures except those containing quinidine gluconate in polyvinyl chloride containers. The only visual incompatibility observed was in admixtures containing quinidine gluconate and 5% dextrose injection. In most solutions pH either decreased slightly or remained unchanged. Amiodarone hydrochloride is stable when mixed with either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers alone or with potassium chloride, lidocaine, procainamide, verapamil, or furosemide and stored for 24 hours at 24 degrees C. Amiodarone should not be mixed with quinidine gluconate in polyvinyl chloride containers.
We describe a "high-performance" liquid-chromatographic assay for quantifying cefamandole in biological fluids from patients with renal impairment. Serum samples are deproteinized with acetonitrile, then extracted with dichloromethane; dialysis-fluid samples are injected directly; urine samples are diluted appropriately before injection onto the reversed-phase column. The mobile phase is a methanol/aqueous solution (31/69 by vol) containing 500 microL of phosphoric acid, 20 mmol of sodium sulfate, and 200 microL of triethylamine per liter, the mixture being adjusted to pH 6.0 with NaOH. Retention time for cefamandole is 12 min. Its peak is well resolved in highly contaminated samples from renally impaired subjects. The assay's selectivity, reproducibility (within-day and between-day CVs less than 8% in all three sample fluids), and sensitivity--0.5 mg/L in serum, 1.0 mg/L in dialysis fluid, and 5.0 mg/L in urine--make it applicable to pharmacokinetic studies.
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Cimetidine does not slow the disappearance of ibuprofen from the serum after a single dose in healthy male volunteers. This suggests that no change in ibuprofen dosing is necessary when cimetidine is co-administered.
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