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Biomedical subjects

J Vessman

Publications and source records attributed to J Vessman.

At least 37 records · Page 2Linked to original sources

Evaluation of some critical factors affecting determination of aluminum in blood, plasma, or serum by electrothermal atomic absorption spectroscopy.

A digestion procedure involving nitric acid is described for determination of aluminum in blood, serum, and plasma by graphite-furnace atomic absorption spectroscopy. Contamination was not a severe problem if all operations were performed in a dust-free atmosphere. Conditions for such determination of aluminum in blood were optimum when the L'vov platform technique was used and hydrogen added to the inner gas flow of the furnace. We discuss the importance of adequate correction for nonspecific absorbance when this technique is used close to the detection limit. The blank value for the overall procedure was 1.0 (SD 0.59) micrograms/L (n = 22). We applied the method to frozen whole blood, plasma, and serum samples. For whole-blood samples from 11 different healthy subjects the mean value was as low as 1.6 (SD 1.29) micrograms of AI per liter (n = 22).

Aluminum↗

Pharmacokinetics and bioavailability of tranexamic acid.

Tranexamic acid 1 g was given intravenously to three healthy volunteers. Plasma concentrations decayed in three monoexponential phases. Most elimination took place during the first eight hours, giving an apparent elimination half-life of approximately two hours. Plasma clearance ranged between 110-116 ml/min. The urinary recovery of tranexamic acid exceeded 95% of the dose. Ten healthy volunteers were given tranexamic acid 2 g orally on an empty stomach, and together with a meal. Food had no influence on the absorption of tranexamic acid, as judged by comparison of the peak plasma concentration, the time required to reach the peak, the AUC from zero to six hours, and the urinary excretion data. The oral bioavailability of tranexamic acid, calculated from 24 h urinary excretion after oral and intravenous administration, was 34% of the dose.

Administration, Oral↗

Formation of electron-capturing derivatives of alprenolol by transboronation: application to the determination of alprenolol in plasma.

The reaction between 2,4-dichlorobenzeneboronic acid, 3,5-bis(trifluoromethyl)benzeneboronic acid or the 1,3-propanediamine derivatives of the boronic acids and the 3-isopropylaminopropan-2-ol side chain of the beta-blocking drugs occurs essentially as an on-column thermal reaction in the gas phase. Derivatization of the side chain of the beta-blocking drugs by transboronation is shown to be the method of choice for general application as it affects the detector background signal very little compared to the use of the boronic acid itself. The transboronation reaction can be used for the determination of alprenolol in plasma extracts with a detection limit of 2.5 ng ml-1 using the electron-capture detector. The ultimate sensitivity of the method is limited by the detector background signal resulting from some column decomposition of the transboronation reagent.

Alprenolol↗

Analysis of nicotine as a trichloroethyl carbamate by gas chromatography with electron-capture detection.

Nicotine was subjected to reaction at 90 degrees with trichloroethyl chloroformate in the presence of pyridine to form a carbamate in which the pyrrolidine ring was opened. Upon heat treatment, this carbamate partially formed the corresponding olefin. About 10 pg could be detected with an electron-capture detector and 60 pg with an alkali flame-ionization detector. The extraction was studied with 14C-labelled nicotine. Methylene chloride was suitable for extraction from diluted plasma, whereas toluene containing 5% of heptafluorobutanol was used in a re-extraction step and also as the chloroformate reaction medium. Due to a nicotine blank the limit for quantitative determinations was 10 ng/ml in plasma (sample volume 1 ml). N-n-Propylnornicotine was used as an internal standard. The precision at the 30 ng/ml level was +/- 8.8% (n = 7).

Animals↗

gamma,gamma'-(4,4'-Diamino-3,3'-biphenylylenedioxy)dibutyric acid (dicarboxidine) a safer substitute for benzidine type chromogens.

gamma,gamma'-(4,4'-Diamino-3,3'-biphenylylenedioxy)dibutyric acid (dicarboxidine) is a new chromogen developed as a safe substitute for conventional benzidine type reagents. The compound is water soluble and has a low distribution ratio organic phase/aqueous phase, which makes it superior for use with automatic analytical instruments. The stability of both dicarboxidine and its coloured oxidized form are better than and their sensitivity equal to that of o-dianisidine. Dicarboxidine is not mutagenic in Ames test. Studies in mice for two years failed to reveal any carcinogenic activity, studies in rats indicated only a marginal effect.

Aminobiphenyl Compounds↗

Disposition of three benzodiazepines after single oral administration in man.

Three benzodiazepines in equipotent doses: oxazepam 15 mg, dipotassium chlorazepate 10 mg and diazepam 5 mg, were administered in single, oral doses to seven healthy volunteers in a three-way cross-over study. The serum concentrations of oxazepam, N-desmethyldiazepam and diazepam were followed for 72 hours by gas chromatography and electron capture detection. The absorption of diazepam was most rapid and the mean time required to reach peak serum concentration was 45 minutes, followed by N-desmethyldiazepam 80 minutes and oxazepam 114 minutes. The serum concentration decay curves were biphasic with terminal mean half-lives of 48, 62 and 11 hours for diazepam, N-desmethyldiazepam and oxazepam, respectively. The mean and individual serum concentration time data were fitted to a two-compartment open model with first order absorption using a non linear least square program. The mean serum data fitted the model well. The same rank order was obtained with mean absorption half-lives as when comparing mean peak times while slightly shorter terminal half-lives were obtained in the curve fitting of mean serum data. Due to irregularities in the serum concentration time curves only five out of the 21 sets of individual data could satisfy the convergence criterion. The obtained parameters in the curve fitting were also accompanied with very large asymptotic standard deviations.

Administration, Oral↗

First pass conjugation and enterohepatic recycling of oxazepam in dogs; intravenous tolerance of oxazepam in propylene glycol.

Oxazepam dissolved in propylene glycol was administered intravenously to dogs. There were no cardiac or general adverse effects. Hemolysis and thrombophlebitis were observed after rapid infusion (5.6 ml in 1 minute), and were shown to be due to the properties of the vehicle. Comparison of plasma concentration time curves after oral and intravenous administration indicated a bioavailability of 70 +/- 15 S.D. %. The decreased availability after oral dose was considered to be due to first pass elimination as the urinary recovery of metabolites was the same after the two routes of administration. This also indicates complete absorption. In a dog with a chronic biliary fistula 15 mg of oxazepam was given intravenously on two occasions. When normal bile flow into the gut was permitted the disposition of oxazepam was similar to that in normal dogs. When bile was withdrawn the elimination of oxazepam was more rapid with an increase of apparent plasma clearance. In this case 32% of the dose was excreted as conjugates in the bile within 3 hours after administration. In the normal dogs 2-20% of the dose given was recovered in the faeces as the parent compound and practically no conjugates were found. These findings indicate enteral hydrolysis of the conjugates, and a marked enterohepatic recycling or oxazepam.

Administration, Oral↗

Pharmacokinetics of oxazepam in healthy volunteers.

The pharmacokinetics of oxazepam was studied in healthy volunteers. When oral doses of 15 mg were given to eight subjects on two occasions 2.5 years apart the individual areas under the plasma concentration time curves did not differ significantly. Plasma clearance ranged between 0.050 and 0.171 x kg-1 x h-1 and half-lives from 5.9 to 25 hours. The urinary recovery of oxazepam conjugates was 67 +/- 15 S.D.% of the dose given and the total recovery including faecal oxazepam was 70 +/- 15 S.D. %. On multiple dosing (5 mg t.i.d.) stable steady-state concentrations were established. There was a tendency for slightly lower steady-state concentrations than predicted from single oral doses. During steady-state 86 +/- 17 S.D. % of the dose was recovered in the urine over a 24 hour period.

Administration, Oral↗

Oxazepam disposition in uremic patients.

The pharmacokinetics of oxazepam was investigated in 13 uremic patients. The apparent terminal half-life of oxazepam in plasma was 24-91 hours compared to 5.9-25 hours reported elsewhere for healthy volunteers. The plasma concentrations showed secondary peaks about 24 hours after the dose and this probably gave rise to the increase in half-life. Plasma clearance of oxazepam appeared to be normal. The conjugated metabolites accumulated to concentrations 5-50 times those of the parent compound and could still be detected 5 days after a single oral dose (0.2 mg/kg). Renal clearance of conjugated oxazepam was significantly correlated to creatinine clearance. The urinary recovery over 5 days was 18-57%. The faecal recovery of 3 days was 0.1-19%. In some patients up to 49% of oxazepam in faeces was in the conjugated form. It is concluded that enterohepatic recycling of oxazepam might occur in uremic patients but is not of great quantitative importance. During multiple dosing the accumulation of conjugates was even more pronounced, with plasma concentrations amounting to 14-61 times those of oxazepam. Steady-state plasma concentrations of oxazepam was similar to those obtained in normal subjects.

Administration, Oral↗

Comparative bioavailability of oral dosage forms of oxazepam--correlation with in vitro dissolution rate.

Four oxazepam tablet preparations and a suspension of micronized oxazepam in water were given to healthy, fasting volunteers in a comparative bioavailability study using a partial cross-over design. Urinary recovery (0-72 hours) was used as a measure of extent of absorption. Peak serum concentration was used as a measure of rate of absorption. The three dosage forms having the highest dissolution rate in vitro were absorbed to the same extent, while slower dissolving tablets were not as fully absorbed. Peak serum concentration correlated linearly with in vitro dissolution rate. Single oral doses of oxazepam tablets containing 10, 15 and 25 mg showed equal rates and extents of absorption and produced serum concentrations linearly correlated with dose.

Administration, Oral↗

Bioavailability of oxazepam: absence of influence of food intake.

The possible influence of food intake on the bioavailability of the anxiolytic drug oxazepam was assessed in eight healthy volunteers taking a single dose of the drug both on an empty stomach and together with a standardized breakfast meal. The serum concentrations of oxazepam were determined by gas chromatography on samples obtained before, and at numerous occasions up to 48 hours after drug administration. The results indicate that concomitant food intake has no essential influence on the bioavailability of oxazepam.

Adolescent↗

Electron-capture GC determination of subnanogram amounts of emepronium bromide in serum.

Barium peroxide in an acidic medium was utilized to increase the sensitivity in the benzophenone method for the determination of the quaternary ammonium compound emepronium bromide. The method is comprised of ion-pair extraction, oxidation, and quantitative determination of benzophenone by electron-capture GC. By employing small extraction and reaction volumes, the method was used in the 0.2--8-ng/ml range with a relative standard deviation of 2.5% at the 1-ng/ml level. The application of the method to human serum samples after a single oral dose demonstrated that the elimination phase for emepronium in serum had a half-life of 7--11 hr.

Administration, Oral↗

GLC determination of nicotinamide in multivitamin formulations after conversion to nicotinonitrile.

A method was developed for the quantitative GLC determination of nicotinamide. It is based on the conversion of nicotinamide to nicotinonitrile. This dehydration reaction is mediated with trifluoroacetic anhydride and catalyzed by base. The GLC properties of this nitrile are excellent. The reaction conditions, extraction, and stability properties of the derivative as well as the choice of internal standard are discussed.

Anhydrides↗