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Biomedical subjects

M Mayersohn

Publications and source records attributed to M Mayersohn.

At least 91 records · Page 5Linked to original sources
PubMed1982

Allopurinol kinetics and bioavailability. Intravenous, oral and rectal administration.

Six normal, healthy adult males received a single dose of allopurinol intravenously, orally in the form of a commercial tablet, and rectally in the form of an extemperaneously prepared suppository (either in a cocoa butter or in polyethylene glycol base). Plasma allopurinol and oxipurinol concentrations were measured over a period of at least 60 h. The following mean (+/- SD) values were obtained from the intravenous allopurinol experiment: clearance, 9.62 +/- 3.49 ml . kg-1 . min-1; Vd, 1.61 +/- 0.74 l/kg; t1/2, 1.62 h. Oxipurinol had a mean t1/2 of 16.90 h. The absolute systemic bioavailability of the oral tablet was 67% +/- 23%, while the allopurinol rectal suppositories produced no measurable plasma concentrations of allopurinol or oxipurinol in any of the subjects. Current use of rectal dosage forms as an adjunct in cancer chemotherapy should therefore be re-examined.

Administration, Oral↗
PubMed1982

The "Xylose test" to assess gastrointestinal absorption in the elderly: a pharmacokinetic evaluation of the literature.

A pharmacokinetic evaluation has been made of the literature that has examined xylose absorption as a function of age. Urinary xylose recovery during a 5-hour collection declines with age after oral and intravenous dosing. Calculated values for xylose renal clearance and elimination rate constant display a similar dependence upon age. The ratio of urinary recoveries after oral compared with intravenous dosing remains constant up to age 65 years but decreases after 70 years. Age appears to explain most of the variation associated with the above parameters. This analysis supports the suggestion made previously by several investigators that the xylose test as currently used to assess absorption in the elderly has not been properly interpreted.

Adult↗
PubMed1982

Thiopental disposition as a function of age in female patients undergoing surgery.

The effect of age on the disposition kinetics of thiopental was studied in 22 lean female patients having a body mass index (weight (kg/height(m)2) less than 30 and whose age ranged between 25 to 83 years. Patients underwent primarily abdominal surgery. A strong positive correlation between age and the apparent volumes of distribution, V beta and Vss, was found (P less than 0.001). No significant relationship was found between total body clearance and age. The elimination half-life (t1/2) of thiopental increased with age, and was primarily a function of volume of distribution. The free or unbound fraction of thiopental in serum (alpha) ranged between 0.168 and 0.276 and was significantly correlated with age (P less than 0.005). Multiple regression analysis indicated that age was the independent variable which contributed most the variability in t1/2, V beta, and Vss. No conclusion can be reached concerning the potential differences in anesthetic induction doses required as a function of age; however, these data suggest that care may be required in the use of a balanced anesthetic technique in the elderly as a result of prolonged elimination.

Abdomen↗
PubMed1982

Thiopental disposition in lean and obese patients undergoing surgery.

The effect of obesity on the disposition kinetics of thiopental was studied in seven morbidly obese (age 25 to 46 years) and eight age-matched lean patients (age 25 to 43 years), undergoing primarily abdominal surgery. Based upon total (bound + free) thiopental concentrations, the average (+/-SD) volumes of distribution in the terminal disposition phase and at steady-state (V beta and V ss) were significantly larger in the obese (7.94 +/- 4.55 1/kg and 4.72 +/- 2.73 1/kg, respectively) than in the age-matched lean patients (1.95 +/- 0.63 1/kg and 1.40 +/- 0.46 1/kg, respectively). Clearance of total thiopental, normalized for total body weight was not significantly different between the obese (0.18 +/- 0.081 . h-1 . kg-1) and lean patients (0.21 +/- 0.06 1 . h-1 . kg-1). However, total body clearance not normalized for total body weight was significantly larger in the obese (24.98+/- 14.87 1/h) than in the lean patients (11.86 +/- 3.66 1/h). The elimination half-life of thiopental was significantly longer in the obese (27.85 h) than in the lean patients (6.33 h) and this difference was primarily a function of a larger apparent volume of distribution for thiopental. The unbound fraction of thiopental in serum (range, 17.8 per cent to 27.6 per cent) was not correlated with the degree of obesity. The most appropriate means of comparing intrinsic metabolizing capacity (i.e., normalized vs. non-normalized for weight) between lean and obese subjects remains unresolved.

Abdomen↗
PubMed1982

Radioimmunoassay for phencyclidine (PCP) in serum.

This accurate, sensitive radioimmunoassay for determining phencyclidine concentrations in serum specimens involves the use of anti-phencyclidine sera, 0.1 mL of serum specimen, an iodinated tracer, and a solid-phase separation. Phencyclidine metabolites do not show significant cross reactivity, but several phencyclidine analogs do cross react. Within-run coefficients of variation for human and dog serum ranged from 2.5 to 13% for concentrations from 2.0 to 500 micrograms/L. Day-to-day coefficients of variation for human and dog serum ranged from 4.3 to 16.7% for concentrations ranging from 2.0 to 90.0 micrograms/L. The sensitivity of the radioimmunoassay is less than 0.5 micrograms/L. Thirty serum specimens from two dogs given 1 mg of phencyclidine per kilogram body weight were analyzed by radioimmunoassay and a gas-chromatographic method. Nonparametric statistical comparison and linear regression showed that results from the two procedures correlate well (r2 = 0.952). Concentration-time data from the two dogs are presented to illustrate the utility of the radioimmunoassay for examining phencyclidine disposition.

Animals↗
PubMed1981

Assessment of beta blockade with propranolol.

Each of seven subjects received on a weekly basis placebo or 10, 20, 40, 80, or 160 mg propranolol orally four times daily. The effect of propranolol on the resting heart rate and the heart rate responses to the Valsalva maneuver, tilt, isoproterenol, and maximal exercise were measured. Coefficients of determination were calculated from the individual dose-response curves. The results indicate that the resting heart rate and the tachycardiac response to the Valsalva maneuver and tilt cannot be used to estimate beta blockade. Propranolol concentrations correlated well (mean r2 = 0.80) with the isoproterenol dose ration minus one, but isoproterenon challenges appear clinically inapplicable. Reduction in maximal exercise tachycardia correlated best with propranolol concentrations (mean r2 = 0.89) but, to the extent that exercise could not be performed, there was no reliable way of clinically documenting beta blockade and only the serum concentration of propranolol was available as an indicator of appropriate therapy.

Administration, Oral↗
PubMed1981

Digoxin bioavailability during quinidine administration.

Digoxin serum concentration rises in the presence of quinidine. To determine whether quinidine alters digoxin bioavailability, six subjects received 1.0 mg of digoxin intravenously alone and by mouth on alternate weeks during steady-state oral quinidine administration. The area under the digoxin concentration:time curves (AUC) and the amount of digoxin excreted in the urine (Xxu) were determined for the 96 hr after each of the four experiments. Values for digoxin bioavailability relative to the corresponding intravenous study in the absence and presence of quinidine were (+/- S.D.) 73.5 +/- 8.6% and 79.5 +/- 22.6% (P greater than 0.05) for serum and 69.8 +/- 6.8% and 70.2 +/- 10.5% (P greater than 0.05) for urine. There was no difference in the steady-state quinidine serum concentration during the 4 days after intravenous and oral digoxin. We conclude that quinidine does not alter digoxin bioavailability and therefore that altered absorption does not explain the rise in digoxin serum concentration in the presence of quinidine.

Adult↗
PubMed1981

Beta adrenergic blockade with propranolol in conscious euthyroid and thyrotoxic calves: dosage requirements and effects on heart rate and left ventricular performance.

The effects of acute beta adrenergic blockade were studied in nine calves which had been instrumented with sonomicrometer crystals and pressure transducers before and after treatment with thyroxine (200 micrograms/kg) for 14 days. The adequacy of beta adrenergic blockade was determined using graded doses of isoproterenol. The results indicated that beta adrenergic blockade had no significant effect on heart rate, left ventricular dimensions or contractile performance in either thyroid state. However, the average dose of propranolol required to achieve beta adrenergic blockade was increased two to three times by thyroxine treatment. Consequently, the kinetics of propranolol disposition were determined in nine animals after a single i.v. dose of the drug. Also, propranolol was administered to four animals by continuous i.v. infusions at graded dosages to produce a range of serum concentrations in each animal. The amount of isoproterenol required to increase the heart rate by 25 beats/min was determined at each dosage level. It was found that in thyrotoxic animals two to three times higher serum propranolol concentrations were required to block challenge doses of isoproterenol. This could not be explained by changes in the disposition of propranolol. The possibility that there are larger numbers of functionally inactive (uncoupled) beta adrenergic receptors in thyrotoxic myocardium is discussed.

Animals↗
PubMed1981

Gas-chromatographic assay for thiopental in plasma, with use of a nitrogen-specific detector.

An accurate, sensitive, and specific gas-liquid-chromatographic procedure is described for determining concentrations of thiopental in human plasma. After a double extraction of 0.2 or 1.0 mL of plasma containing phenobarbital as an internal standard, thiopental and the internal standard are derivatized in a polar non-aqueous solvent system with iodomethane. The reaction mixture is then evaporated, the residue reconstituted with ethyl acetate, and 20 microL injected into a 3% OV-17 column of a gas chromatograph equipped with a nitrogen-phosphorus detector. Linearity and reproducibility over the concentration range 25 microgram/L to 10 mg/L in plasma are excellent. The sensitivity and wide range of linearity exhibited by this method permit thorough characterization of the disposition of thiopental after the usual induction doses of 3-4 mg/kg of body weight.

Blood Chemical Analysis↗
PubMed1981

The "ultra-free" ultrafiltration technique compared with equilibrium dialysis for determination of unbound thiopental concentrations in serum.

We compare a new ultrafiltration technique, involving a unique Millipore membrane, with the classical method of equilibrium dialysis for determining the fraction of thiopental not bound to serum proteins. This fraction, as determined by equilibrium dialysis at 37 degrees C, ranged between 12 and 16% for total concentrations at 50 microgram/L to 10 mg/L of serum. In contrast, ultrafiltration at 37 degrees C yielded a 49% higher value for unbound thiopental: 26.3 (SD 2.6)%. Determined at room temperature (24 degrees C), there was no statistically significant difference for results by the two methods: 14.2 and 15.9%, respectively. The discrepancy between results at 37 degrees C may partly be explained by serum proteins penetrating the Ultra-Free filter. For the routine clinical measurement of unbound drug concentrations, the ultrafiltration membrane at room temperature appears to be sufficiently accurate and less time-consuming than equilibrium dialysis.

Blood Chemical Analysis↗
PubMed1980

Efficacy, plasma concentrations and adverse effects of a new sustained release procainamide preparation.

To assess the efficacy, plasma drug concentrations and adverse effects of a new sustained release preparation of procainamide, 33 patients with heart disease were studied in an acute dose-ranging protocol and a chronic treatment protocol. Patients initially received a daily dose of 3 g of sustained release procainamide; this dose was increased by 1.5 g daily until ventricular premature depolarizations were suppressed by 75 percent or more, adverse drug effects occurred or a total daily dose of 7.5 g of sustained-release procainamide was reached. Twenty-five patients (76 percent) had at least a 75 percent reduction (range 75 to 100percent [mean +/- standard deviation 91 +/- 8.2]) in ventricular permature depolarization frequency at a dosage of 4.8 +/- 1.46 g/day (range 3.0 to 7.5). Despite the 8 hour dosing interval, the variation between maximal and minimal plasma procainamide and N-acetylprocainamide concentrations under steady state conditions was very small. Mean maximal procainamide and N-acetylprocainamide plasma concentrations were 10.4 +/- 6.02 and 12.0 +/- 7.40 micrograms/ml, respectively. The respective mean minimal concentrations were 6.8 +/- 4.50 and 8.7 +/- 5.99 micrograms/ml. In nine patients (27 percent) treatment with sustained release procainamide resulted in conversion of the antinuclear antibody test from negative to positive. Adverse drug effects occurred in 17 (52 percent) of the subjects. In general, adverse effects were minor and abated within 24 hours after administration of the drug was stopped. One patient had the procainamide-induced systemic lupus erythematosus-like syndrome.

Acecainide↗
PubMed1980

Kinetic evaluation of the propranolol-quinidine combination.

The kinetics of quinidine and propranolol, administered singly and in combination, were evaluated in 5 healthy subjects. The orally administered doses resulted in plasma concentrations within the therapeutic range. For each drug the average steady-state plasma concentration, maximal plasma concentration, and time of maximum plasma concentration were not altered by the presence of the other drugs. This study shows no kinetic interaction between quinidine and propranolol in normal subjects.

Adult↗
PubMed1980

Metabolism and rate of elimination of digoxigenin bisdigitoxoside in dogs before and during chronic azotemia.

The purpose of this study was to evaluate the metabolism and rate of elimination of digoxigenin bisdigitoxoside (bis) before and during chronic azotemia in dogs. Bis was eliminated primarily by nonrenal mechanisms. The half-life of bis was 18.5 hr, compared to 31.6 hr for digoxin, and was not significantly increased in azotemic dogs. The oral bioavailability of bis in azotemic dogs relative to an intravenous dose was approximately 46%.

Animals↗