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Biomedical subjects

M Mayersohn

Publications and source records attributed to M Mayersohn.

At least 73 records · Page 4Linked to original sources
PubMed1986

Stability of amiodarone hydrochloride in admixtures with other injectable drugs.

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.

Amiodarone↗
PubMed1986

Disposition kinetics of the monohydroxy metabolites of phencyclidine in the dog.

The monohydroxy metabolites of phencyclidine (PCP) have been suggested to contribute to the pharmacologic activity of PCP, and perhaps account for its prolonged action. The disposition kinetics of the monohydroxy metabolites of PCP were examined in dogs. Intravenous doses of the piperidine-hydroxylated metabolite (PCHP) and the trans- and cis-forms of the cyclohexyl-hydroxylated metabolite (trans-PPC and cis-PPC) were each administered to three dogs. The elimination half-life of each metabolite was short, with harmonic mean values of 1.29, 0.98 and 0.92 hr for PCHP, trans-PPC and cis-PPC, respectively. The compounds had large volumes of distribution, with average values of 6.7, 4.7 and 4.4 liters/kg for PCHP, trans-PPC and cis-PPC, respectively. Systemic clearances were high for each compound (51.9, 50.9 and 54.2 ml/min/kg for PCHP, trans-PPC and cis-PPC, respectively), but renal clearances were low (average values ranged from 2 to 8% of systemic clearance), suggesting that these metabolites undergo further metabolism. Analysis of acid-hydrolyzed serum and urine samples indicated that all three compounds were conjugated and that these conjugates were the primary metabolites. The conjugated metabolites exhibited elimination half-lives longer than the parent compounds after administration of the monohydroxy forms and after PCP dosing. The disposition of these metabolites suggest that these compounds are not produced in sufficient quantities or do they exhibit pharmacokinetic behavior which would be consistent with the prolonged effects from PCP.

Animals↗
PubMed1986

Liquid-chromatographic assay of cefamandole in serum, urine, and dialysis fluid.

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.

Cefamandole↗
PubMed1985

Gastrointestinal absorption as a function of age: xylose absorption in healthy adults.

Xylose oral absorption was examined in 24 healthy male subjects ranging in age from 32 to 85 years. Absorption was evaluated from xylose plasma concentration-time data after administration of a 25 gm po or a 5 gm iv dose. There was no relationship between various estimates of the rate of absorption and age. The absolute oral bioavailability or the extent of xylose absorption showed no relationship to age in our population. In contrast with previous suggestions, xylose absorption does not decline with age. General statements of decreased gastrointestinal absorption efficiency as a function of age may not be correct.

Administration, Oral↗
PubMed1985

Phencyclidine (PCP) disposition kinetics in dogs as a function of dose and route of administration.

Phencyclidine (PCP) disposition kinetics has been examined in dogs as a function of dose and after i.v. and p.o. administration. Intravenous doses ranged from a tracer quantity of [3H]PCP to 5 mg/kg of unlabeled PCP. The elimination half-life of intact PCP was relatively short with harmonic mean values of 2.7, 5.4 and 3.9 hr for the tracer, 1- and 5-mg/kg doses, respectively. In contrast, measurement of total radioactivity gave a much longer half-life (35-52 hr) suggesting slower metabolite elimination. The drug has a large apparent volume of distribution (weighted mean of 20 liters/kg) and a systemic clearance (which is primarily metabolic) that approaches estimates of liver blood flow in the dog. Renal clearance of intact PCP represents a small fraction of total clearance. Percentage of the [3H]PCP dose recovered as total radioactivity was 49% in urine and 12% in feces. Several metabolites of PCP were determined in urine and they account for about 30% of the dose with the aminopentanoic acid derivative being present in the greatest amount. One of the hydroxylated metabolites is present in cis- and trans-forms, with the latter predominating. Three animals received an i.v. dose of [3H] PCP and a p.o. dose of unlabeled PCP at the same time to determine absolute bioavailability. Approximately 25% of the dose is absorbed intact. The p.o. (intrinsic) clearance of PCP is about four times greater than systemic clearance suggesting a blood flow-dependence in clearance and substantial first-pass hepatic metabolism.

Administration, Oral↗
PubMed1984

Quantitation of xylose from plasma and urine by capillary column gas chromatography.

A specific and sensitive assay for quantitation of xylose from plasma and urine has been developed. Following a clean-up procedure, plasma (0.1 ml) or urine (0.2 ml) samples are concentrated and undergo two sequential derivatization steps. A methyloxime derivative is formed initially, followed by trimethylsilylation of all hydroxyl groups. The derivatized samples are quantitated by capillary column gas chromatography using flame ionization detection. Xylose and the internal standard (2-deoxy-D-ribose) have retention times of 6.5 and 5.2 min, respectively. Other monosaccharides (e.g. ribose, arabinose) do not interfere with the assay. Standard curves are linear and reproducible over a concentration range of 10-200 mg/l for plasma and 100-2000 mg/l for urine. The within-day and day-to-day percentage coefficients of variation were less than 5 and 9%, respectively, for plasma and urine.

Arabinose↗
PubMed1984

Analysis of 4-methylpyrazole in plasma and urine by gas chromatography with nitrogen-selective detection.

A simple, sensitive, and specific gas chromatographic method for the quantitation of 4-methylpyrazole in plasma and urine is described. Samples containing 4-methylpyrazole, with 3-methylpyrazole as the internal standard, are extracted into ether and the concentrated ethereal extracts are chromatographed on a Carbowax 20M column using nitrogen-selective detection. Standard curves are linear and reproducible over the range of 25-1000 ng/mL for plasma and 0.5-5 micrograms/mL for urine. Recovery of 4-methylpyrazole is complete from plasma and urine, and the overall between-day coefficient of variation is within 6.0%. No interference is observed from the extractive constituents of plasma and urine. The assay method is suitable for an examination of 4-methylpyrazole disposition in animals and humans.

Animals↗
PubMed1983

HPLC analysis of creatinine in human plasma and urine.

A simple, rapid, reproducible HPLC method is described for the analysis of creatinine in human plasma and urine. Creatinine is isolated from plasma proteins prior to HPLC analysis by ultrafiltration using a micropartition system. The technique requires only 0.2 ml of plasma and the recovery of creatinine is complete. Results from the HPLC analysis are compared with those from an automated (colorimetric) analysis. The retention time of creatinine is 2.6 min.

Autoanalysis↗
PubMed1983

The influence of a cooked meat meal on creatinine plasma concentration and creatinine clearance.

1 The influence of a meal containing cooked meat (225 g) on creatinine plasma concentration, creatinine urinary excretion and creatinine clearance was determined in six healthy male subjects. 2 The meat meal produced an average 52% increase in creatinine plasma concentration within 1.5 to 3.5 h after ingestion. The 24 h area under the creatinine plasma concentration-time curve increased by about 19%. Urinary creatinine excretion during 24 h increased by an average of 13%. Creatinine clearance was not altered in response to the meal of cooked meat.

Adult↗
PubMed1983

Effect of the ouabain-quinidine interaction on left ventricular and left atrial function in conscious dogs.

The effect of the ouabain-quinidine interaction was examined in 10 conscious dogs. Left ventricular (LV) pressure, LV dP/dt, LV diameter and left atrial (LA) diameter were measured with high-fidelity micromanometers and sonomicrometer crystals. Ouabain, 0.025 mg/kg, significantly (p less than 0.05) increased LV dP/dt, LV and LA fractional shortening and LV and LA velocity of circumferential fiber shortening (Vcf). In a separate experiment, quinidine was administered as a bolus dose, 3.85 mg/kg, followed by an infusion, 0.28 mg/kg/min. This resulted in steady-state quinidine concentrations that produced no change in wall motion or hemodynamics. When ouabain was given 1 hour into the quinidine infusion, only LV dP/dt increased significantly (p less than 0.05). Ouabain alone increased LV dP/dt 26.4 +/- 3.5%, whereas ouabain during the quinidine infusion increased it by 9.5 +/- 2.3%. Similar differences were seen in the responses to ouabain in the absence and presence of quinidine: LV Vcf, 22.4 +/- 4.9% vs 6.0 +/- 2.1%, LV fractional shortening, 23.1 +/- 4.6% vs 5.8 +/- 2.1%, LA Vcf, 22.7 +/- 5.9 vs 4.6 +/- 2.0% and LA fractional shortening, 21.8 +/- 7% vs 7.8 +/- 3.3%. Thus, in the presence of quinidine the increase in intropy usually seen with ouabain was markedly attenuated. These data suggest that the quinidine-induced increase in digoxin serum concentrations is accompanied by a decrease in the contractile response of the heart to digoxin.

Animals↗
PubMed1983

Phencyclidine blood protein binding: influence of protein, pH and species.

We studied the influence of protein, pH and species on phencyclidine (PCP) protein binding. PCP binding to dog serum was unaffected by high concentrations of PCP and metabolites. The percentage of unbound PCP in pooled human serum and plasma specimens and pooled dog serum specimens was (mean +/- S.D.): 48.3 +/- 2.5; 42.5 +/- 1.8; and 43.3 +/- 1.9%, respectively. The percentage of unbound PCP in human serum albumin (HSA), 81.2 +/- 2.0%, was constant over the physiological HSA concentration range (3.5-5.5 g/dl). The binding of PCP to alpha 1-acid glycoprotein (alpha 1-AGP) increased with increasing alpha 1-AGP concentration (50-200 mg/dl). The binding to HSA or alpha 1-AGP separately did not account for the binding found in whole serum or plasma specimens. However, when a constant concentration of HSA (4.5 g/dl) was added to varying concentrations of alpha 1-AGP, the PCP binding increased dramatically and was similar to the binding found in human serum specimens. The association constant in the presence of both proteins (7.72 X 10(4) M-1) was 4.4 times greater than the association constant for alpha 1-AGP alone (1.74 X 10(4) M-1). This suggested an interaction between the proteins which resulted in enhanced PCP binding. The percentage of unbound PCP increased with decreasing pH in both dog serum and human serum specimens. This change could have possible effects on PCP distribution and elimination. The PCP blood to plasma ratio was 0.94 in pooled human heparinized blood and 1.25 in pooled dog heparinized blood. Neither species showed PCP concentration-dependent partitioning.

Animals↗
PubMed1982

Ascorbic acid absorption in humans: a comparison among several dosage forms.

There have been few studies conducted to determine the efficiency of ascorbic acid absorption in humans. Differences in the extent of its absorption among individuals may contribute to the outcome of clinical trials. Ascorbic acid absorption in four subjects was investigated from several oral dosage forms containing 1 g of the vitamin (solution, tablet, chewable tablet, and timed-release capsule. Approximately 85% of an intravenous dose was recovered in the urine as ascorbic acid and its major metabolites. In contrast, only approximately 30% of the dose was recovered from the solution and tablet forms. A considerably smaller fraction of the dose (approximately 14%) was recovered from the timed-release capsule. There was considerable intersubject variation in ascorbic acid absorption and there appeared to be good and poor absorbers of the vitamin. Consideration should be given to the influence of the extent of ascorbic acid absorption on the results of clinical trails.

Adult↗