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Biomedical subjects

M Mayersohn

Publications and source records attributed to M Mayersohn.

At least 19 recordsLinked to original sources
PubMed1992

Inhibitory effect of 4-methylpyrazole on antipyrine clearance in rats.

Pyrazole and 4-methylpyrazole (4-MP) are potent, effective inhibitors of alcohol dehydrogenase. Pyrazole and its derivatives also have been shown to affect the cytochrome P-450 dependent monooxygenase system. This study was performed to investigate the effect of 4-MP on the disposition kinetics of antipyrine (AP). Groups of male Fisher 344 rats were given an ip injection of 4-MP (100 mg/kg) or 4-MP HCl (equivalent to 4-MP 100 mg/kg) or an equivalent volume of saline. AP (20 mg/kg) was injected intravenously via the jugular vein catheter 30 minutes later. Blood samples were collected upto 24 hours and assayed by HPLC. 4-MP pretreatment significantly decreased AP clearance from 0.490 +/- 0.032 to 0.095 +/- 0.014 (4-MP HCl) and 0.076 +/- 0.008 (4-MP) L/hr.kg (p less than 0.01). The volume of distribution of AP decreased from 0.82 +/- 0.07 to 0.65 +/- 0.06 (4-MP HCl) and 0.56 +/- 0.04 (4-MP) L/kg (p less than 0.05). Mean residence time increased from 1.68 +/- 0.09 to 6.91 +/- 0.58 (4-MP HCl) and 7.39 +/- 0.56 (4-MP) hr (p less than 0.01). These results demonstrate a significant inhibitory effect of 4-MP on the cytochrome P-450 isozyme(s) which is responsible for AP metabolism in intact animals.

Animals↗
PubMed1992

Effects of constriction bands on rattlesnake venom absorption: a pharmacokinetic study.

STUDY OBJECTIVE: To determine whether the use of a constriction band alters systemic absorption of rattlesnake venom in pigs and whether constriction band use alters local swelling. DESIGN: Using a crossover design, five pigs were studied with and without the use of a constriction band. 125I-Labeled Western Diamondback rattlesnake (Crotalus atrox) venom was injected subcutaneously into one foreleg. The protocol was repeated using the opposite foreleg six days later. The constriction band was applied at the time of injection and removed four hours later. Plasma radioactivity and leg circumference were measured serially. RESULTS: Maximum plasma venom concentration and area under the venom concentration-time curve were compared in trials with and without constriction band. Within the initial four hours, application of a constriction band decreased maximum plasma venom concentration by 25% and area under the venom concentration-time curve by 33% (P less than .05). After the constriction band removal at four hours, maximum plasma venom concentration and the area under the venom concentration-time curve were not significantly different between groups. Application of a constriction band did not result in a statistically significant increase in maximum leg circumference as compared with trials without a constriction band. CONCLUSION: The use of a constriction band was effective in reducing venom absorption while it was in place (reduced area under the venom concentration-time curve and maximum plasma venom concentration in the cuffed group), and constriction band removal did not result in a significant increase in maximum plasma venom concentration. Leg swelling was not affected by constriction band use. Because constriction band use delayed venom absorption without causing increased swelling, it may prove to be a useful first aid measure in human beings.

Absorption↗
PubMed1992

Vitamin C bioavailability.

The above brief review indicates that the bioavailability of vitamin C in humans is complex and that our current understanding of that process and factors that influence it are incomplete. It is important that an overall pharmacokinetic scheme be developed and tested to completely describe the complex dispositional and absorption processes of the vitamin. Such information will provide a better understanding of the absorption and disposition of the vitamin per se. Furthermore, that information will permit us to better understand how those factors influence the participation of the vitamin in events associated with maintenance of health.

Administration, Oral↗
PubMed1991

The influence of age on salicylate pharmacokinetics in humans.

The pharmacokinetics of salicylate after a single oral solution dose of 600 mg of sodium salicylate were investigated in 22 male subjects. Subjects were healthy nonsmokers and were not taking any regular medication. The plasma concentration and urinary excretion of salicylic acid and its metabolite, salicyluric acid, as well as the urinary excretion of salicyl glucuronides were determined. Urinary recovery essentially accounted for the administered dose and was not influenced by age, nor was the apparent oral clearance of salicylic acid. Assuming no presystemic elimination, it could be concluded that systemic availability is unaffected by age. An increase in the apparent volume of distribution, Varea, and a decrease in the maximum plasma salicylic acid concentration with age were observed. Renal clearance of salicyluric acid decreased significantly with age and was found to correlate significantly with creatinine clearance. The authors conclude that age does not have a major influence on salicylate disposition in healthy adult men.

Administration, Oral↗
PubMed1991

Area-based estimation of the initial volume of distribution and elimination rate constant following intravenous bolus injection.

We evaluate here an area term, the area under the rate of change of concentration-time curve (AURC), which allows the determination of the initial or central volume of distribution (V1). It has previously been shown that AURC is equal to the sum of the coefficients of a multiexponential equation and, therefore, V1 = dose/AURC. It is also shown that the normalized moment, AURC/AUC, is equal to the elimination rate constant, K10, where AUC is the area under the concentration-time curve. This area-based method to estimate V1 and K10 has been evaluated with simulation of three model equations and compared with nonlinear regression analysis of the same data. Random errors of 10 and 15% were introduced into the concentration values. The AURC method provides values of both parameters that are similar to those obtained from nonlinear regression analysis and which are reasonably accurate estimates of the theoretically correct values. The potential limitations of this area method are discussed. Good correlations were also observed for values of V1 and K10 obtained by AURC and regression methods for data obtained from the literature for 13 different drugs.

Female↗
PubMed1991

The preparation and evaluation of a tablet dosage form of cyclosporine in dogs.

Cyclosporine (CsA) is commercially available for oral administration as a solution in olive oil with alcohol and an emulsifier. To improve its variable absorption and low patient acceptability, several oral formulations were prepared and tested in vitro and in vivo in dogs. A tablet formulation prepared by direct compression was then selected for comparison with the commercial oil solution placed into soft gelatin capsules. The study involved a randomized crossover design in six dogs. In order to determine absolute bioavailability and to compensate for any time-dependent changes in clearance, an intravenous tracer dose of 3H-CsA was administered along with each oral test product on each of two occasions. Absolute bioavailability (mean +/- SD) was 46.0 +/- 11.1 and 45.4 +/- 9.9% for the capsules and tablets, respectively. Cmax, tmax, and mean absorption time were not significantly different between the two products. No differences were observed in the pharmacokinetics of the intravenously administered CsA in the two experiments, which were separated by 8-13 days. We conclude that the proposed tablet formulation for CsA is equivalent in dogs to the commercial dosage form placed into soft gelatin capsules.

Administration, Oral↗
PubMed1991

Cimetidine alters the disposition kinetics of the monoamine oxidase-A inhibitor moclobemide.

The influence of cimetidine on the absorption and disposition of moclobemide was examined in eight healthy male subjects. A single 100 mg intravenous and 100 mg oral dose of moclobemide was administered before and after 2 weeks of cimetidine administration (200 mg five times a day). The data on intravenous administration indicated that cimetidine produced a statistically significant alteration in the following disposition parameters (mean values for control versus cimetidine): systemic clearance, 46.6 versus 28.3 L/hr; mean residence time, 2.1 versus 3.2 hours; elimination half-life, 1.6 versus 2.3 hours. There was no significant difference in the steady-state volume of distribution. The absolute oral bioavailability of moclobemide increased significantly after cimetidine administration (54% versus 68%), as did the maximum plasma concentration after a single oral dose (575 versus 787 ng/ml). There were no differences in the mean absorption time or time to achieve maximum concentration. The values of systemic and apparent oral clearances of moclobemide after cimetidine administration were directly related to the corresponding control values before cimetidine. In contrast, the percentage change in clearance was essentially independent of the corresponding initial control clearance value.

Adult↗
PubMed1990

Disposition kinetics of moclobemide, a new MAO-A inhibitor, in subjects with impaired renal function.

A single intravenous and oral dose of moclobemide (Ro 11-1163) was administered to 13 subjects with varying degrees of renal impairment (creatinine clearances ranging from 0 to 40 mL/min). The resulting disposition and absorption parameters of moclobemide were more variable than but, with the exception of mean absorption time, were not significantly different from values obtained in another study conducted in 12 normal healthy subjects. There were no relationships between any of the disposition parameters and renal function as measured by creatinine clearance. The disposition of two metabolites of moclobemide were partially characterized from plasma data. One of these (Ro 12-8095) appears to be formation rate-limited and, from available data, behaves in a manner similar to what has been observed in normals. The other metabolite (Ro 12-5637) has a long apparent disposition half-life and is present in greater concentrations in the renally impaired compared to the normal subjects. The latter observation may reflect reduced elimination clearance in the renally impaired subjects. Based upon the results of this study there does not appear to be any need to alter the normal dosing regimen of moclobemide in subjects with renal impairment in order to achieve drug concentrations similar to those in healthy subjects.

Administration, Oral↗
PubMed1990

Absorption and disposition of moclobemide in patients with advanced age or reduced liver or kidney function.

Three different studies were conducted to assess the pharmacokinetics of moclobemide in subjects with conditions complicating dose determination. The first examined the absorption and disposition of moclobemide in an elderly population and compared these with results obtained in a group of normal young subjects. No significant differences were found between the groups in the intravenous (i.v.) parameters of disposition, and no differences with regard to disposition of the metabolite, Ro 12-8095. In addition, the minimum steady-state concentrations of moclobemide and the main plasma metabolite did not differ between the elderly and younger patients. In the second study, clearance tests in patients with cirrhosis of the liver confirmed that hepatic function is drastically reduced in this group of patients; it is therefore possible that moclobemide absorption and distribution might be influenced. In only 3 of the 12 patients investigated, slowly declining plasma concentrations after administration pointed to a severely limited elimination capacity for moclobemide. In the remaining 9 subjects, average values of several parameters changed significantly (t 1/2 beta, MRT and C1), whereas Vss and renal clearance were not significantly altered. In patients with kidney dysfunction, there were no differences in kinetics between patients undergoing hemodialysis and those who were not. Compared with normal healthy volunteers, no differences were found for renal patients, with the exception of the mean absorption time, which was significantly prolonged. From these studies it can be concluded that, pharmacokinetically, neither age nor renal impairment require adjusting the dosage of moclobemide. Patients with liver cirrhosis, however, need to have the usual dose reduced to one half or one third, or else the dosage intervals can be increased to prevent cumulation.

Administration, Oral↗
PubMed1979

Digoxin-quinidine interaction Pharmacokinetic evaluation.

Several recent reports have shown that plasma concentrations of digoxin increase when quinidine is administered along with digoxin; the present study was designed to explore the pharmacokinetics of this digoxin-quinidine interaction in six subjects. The elimination half-life of digoxin, although variable, did not change appreciably (42 vs. 44 hours) when quinidine was administered. Other pharmacokinetic values were substantially reduced in the presence of quinidine: total body clearance (from 3.08 to 1.96 ml per minute per kilogram), renal clearance (from 1.64 to 1.09 ml per minute per kilogram) and volume of distribution (from 10.87 to 7.35 liters per kilogram). The results may be explained by the displacement of digoxin from binding sites in tissue by quinidine, causing a rise in the plasma concentration of digoxin. The reduction in renal clearance of digoxin may result also from inhibition of renal secretion of digoxin by quinidine.

Digoxin↗
PubMed1978

Dose tolerance and pharmacokinetic studies of L (+) pseudoephedrine capsules in man.

Dose tolerance and pharmacokinetic studies of pseudoephedrine sustained action capsules were performed in thirty-three adult male subjects who received either 120 mg or 150 mg capsules every twelve hours for seven consecutive days in a double-blind parallel design study. Although only one subject in the 150 mg group was discontinued prematurely from this study, a large number of side effects typical of CNS stimulation were seen. A placebo effect might account for a portion of these complaints, however symptoms evaluated as being due to drug were significantly more severe and persistent in the 150 mg group. Pulse rates showed a persistent and significant increase while systolic and diastolic blood pressure fell from the baseline values in both groups. A pharmacokinetic analysis of the pseudoephedrine plasma concentration-time data provided estimates of half-life and the volume of distribution/availability ratio. The values obtained were in good agreement with values reported by others. Half-life was not influenced by urine pH probably as a result of the narrow range of urine pHs observed in the subjects. Calculations of relative bioavailability suggest that the 120 mg capsule formulation has a 30% greater bioavailability compared to the 150 mg capsule.

Adult↗
PubMed1978

Relationship between plasma concentration and dose of digoxin in patients with and without renal impairment.

The purpose of this study was to determine if there is a linear relationship between oral doses of digoxin and various measurements of steady-state digoxin plasma concentration and urinary excretion in patients with wide range of renal function. Ten patients (mean age 58 years) with creatinine clearances greater than 50 ml/min/1.73 m2 BSA (mean creatinine clearance 80 ml/min/1.73 m2 BSA) and nine patients mean age 61 years) with creatinine clearances less than 50 ml/min/1.73 m2 BSA (mean creatinine clearance 20 ml/min/1.73 m2 BSA) were given digoxin tablets orally at two or three different dose levels (dose range 0.0313--0.5 mg/day). After a dosing period equal to at least five half-lives, three to four consecutive daily digoxin plasma concentrations were determined. Plasma concentrations and urinary digoxin excretion were measured during one 24-hour dosing interval at each dose level. Digoxin plasma and urine concentrations were determined in triplicate using radioimmunoassay. Individual patient plots provided evidence of linearity for: digoxin 24-hour steady-state plasma concentration vs dose; digoxin 24-hour cumulative urinary excretion versus dose; and area under the digoxin plasma concentration-time curve during a 24-hour dosing interval vs dose. Absolute values for these various parameters indicated substantial interpatient variation probably due to patient differences in both digoxin absorption and digoxin total body clearance. These results indicate that there is a linear relationship between digoxin plasma concentration and dose in patients with normal and decreased renal function. This linearity is support for dose-independent pharmacokinetics of digoxin in man. We conclude from these data that a change in digoxin dose should result in a proportional change in digoxin plasma concentration over the dose range examined.

Administration, Oral↗