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Biomedical subjects

H Mascher

Publications and source records attributed to H Mascher.

At least 37 records · Page 2Linked to original sources
PubMed1993

Nonketotic hyperglycinemia: clinical and electrophysiologic effects of dextromethorphan, an antagonist of the NMDA receptor.

A 10-week-old girl with nonketotic hyperglycinemia was treated with increasing amounts of dextromethorphan, an NMDA receptor antagonist. She improved neurologically; at 35 mg/kg/d, seizures ceased and EEG normalized. Dextromethorphan withdrawal resulted in a dramatic clinical deterioration coinciding with epileptic and high-voltage slow activity in the EEG. After reintroduction of dextromethorphan (35 mg/kg/d), recovery occurred within 24 hours.

Amino Acid Metabolism, Inborn Errors↗
PubMed1992

New, high-sensitivity high-performance liquid chromatographic method for the determination of acyclovir in human plasma, using fluorometric detection.

A high-performance liquid chromatographic method for the determination of acyclovir in human plasma has been developed. It is the first published chromatographic method capable of determining acyclovir in plasma with sufficient sensitivity and for sufficiently long periods of time following oral administration of a standard dose of acyclovir during pharmacokinetic investigations. Following precipitations of the proteins with perchloric acid, the sample is chromatographed with a strongly acidic mobile phase on a reversed-phase column, and is then subjected to fluorometric detection (excitation 260 nm, emission 375 nm). The determination limit is 6-10 ng/ml human plasma. The calibration is linear in the range 10-12,400 ng/ml plasma, with the coefficients of variation less than 8%. The absolute recovery rate is between 102 and 113%. This method has already been used to analyse several thousand plasma samples.

Acyclovir↗
PubMed1992

Study on dose-linearity of the pharmacokinetics of silibinin diastereomers using a new stereospecific assay.

Silibinin in single doses of 102, 153, 203 and 254 mg was applied as silymarin in capsules (Legalon 140) to 6 healthy male volunteers. Using a newly developed HPLC method, both diastereomers of silibinin were assayed in plasma as unconjugated compounds as well as total isomers after hydrolysis. In the dose range studied, the areas under the curves correlate linearly with the dose. On average, only 10% of total silibinin in plasma is in the unconjugated form. The ratio of the silibinin isomers is reversed, if unconjugated and total isomers are compared. For unconjugated silibinin, the half-lives are less than one hour, but the terminal half-life has probably not been observed, because already after 4-6 hours the levels fell below the limit of determination of 2.5 ng diastereomer/ml. For total silibinin, an elimination half-life of approximately 6 h is estimated. About 5% of the dose is excreted into urine as total silibinin, corresponding to a renal clearance of approximately 30 ml/min. No adverse events were noted, showing that silymarin even in high doses, up to 5 capsules of Legalon 140, is well tolerated.

Adult↗
PubMed1991

Endogenous plasma N-acetylcysteine and single dose oral bioavailability from two different formulations as determined by a new analytical method.

A method to quantitate N-acetylcysteine in plasma using reductive cleavage with tributylphosphine and post-HPLC column derivatisation with omicron-phthalaldehyde is described. Using this method, endogenous average concentrations of 0.08 microM were measured in 10 volunteers participating in a crossover study to compare the bioavailability of two different formulations of N-acetylcysteine. The drug was detected in plasma for up to 12 h after administration of a single oral dose (200 mg); the Cmax values were up to 20 times the endogenous levels. The sensitivity and selectivity of the method should thus enable the behaviour of N-acetylcysteine after oral administration to be properly described and bioavailability studies to be performed.

Acetylcysteine↗
PubMed1990

Determination of amoxicillin in plasma by high-performance liquid chromatography with fluorescence detection after online oxidation.

A simplified high-performance liquid chromatographic method for the determination of amoxicillin in plasma is described. Specific and sensitive fluorescence detection was achieved by on-line post-column electrochemical oxidation, using an electrochemical detector. Owing to the high specificity of the detection system, deproteinized plasma samples could be injected directly without prior treatment. This method permits a very fast and reproducible determination of amoxicillin in plasma on a routine basis at levels, down to 50 ng/ml. The absolute detection limit is about 10 pg injected.

Amoxicillin↗
PubMed1989

The pharmacokinetics of a new sustained-release form of diclofenac sodium in humans.

In the present study, two sustained release diclofenac preparations were administered every 12 hours over 4 days to ten human volunteers. Diurnal profiles were recorded on the 1st and 4th days, from which pharmacokinetic parameters were calculated: particular attention was given to cumulation. One, a newly developed sustained release formulation, had a MRT of 5.5 hours, and showed surprisingly small variation coefficients [AUC ss (72-84 hrs) +/- 26%; Cmax ss (72-84 hrs) +/- 19%] after 7 administered doses; accordingly, the maximum concentrations were within a very narrow time window [tmax ss (72-84 hrs) range: 1.5-2.5 hours after administration]. Due to the selected release profiles with this formulation, there was no danger of cumulation in spite of administration every 12 hours [AUC 0-12 hrs, mean value = 1555 ng/ml x h; AUC ss 72-84 hrs, mean value = 1750 ng/ml x h].

Adult↗
PubMed1986

Pharmacokinetics and bioequivalence of different formulations of pirenzepine.

An intraindividual comparative single-dose study was carried out under carefully controlled conditions on 12 healthy volunteers in order to establish the bioavailability of 5,11-dihydro-11-[(4-methyl-piperazin-1- -yl)acetyl]-6H-pyrido[2,3b][1,4]benzodiazepin-6-one dihydrochloride (pirenzepine), the active principle of newly developed tablets (Gastricur) and suspension containing 10 mg. In an additional multiple dose, cross-over study on 12 healthy volunteers, the bioequivalence of pirenzepine was investigated after administration of the newly developed vs. commercial dose-equivalent tablets. Pirenzepine was assayed from plasma by a new, highly sensitive high-performance liquid chromatography method. A 3-compartment model was taken as a basis for the calculation of the plasma concentration curves and the pharmacokinetic parameters. Following i.v. administration, the terminal elimination half-life, t 1/2, the volume of distribution, V1, and the total plasma clearance Cl were determined to be 7.7 +/- 1.4 h, 0.255 +/- 0.057 l/kg and 263.4 +/- 56.8 ml/min, respectively. From the tablet and suspension formulation the systemic availabilities were calculated to be 33.5% and 20.3%, respectively. In the multiple dose study, both tablet forms investigated were bioequivalent.

Administration, Oral↗
PubMed1984

Separation, isolation and identification of optical isomers of 1,4-benzodiazepine glucuronides from biological fluids by reversed-phase high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic (HPLC) method for the determination of four separate 1,4-benzodiazepine glucuronides in urine, plasma and bile is presented. We succeeded not only in determining the single glucuronides but also in separating the enantiomers (optical isomers) of the 1,4-benzodiazepine glucuronides. The optical isomers of the glucuronides of oxazepam and cinolazepam and of two other glucuronides of benzodiazepine metabolites could be well separated. The ratio of the isomers could be evaluated. An octadecyl reversed phase was used with a mobile phase of acetonitrile and 0.01 M orthophosphoric acid. After the initial separation, the isomers were fractionated by HPLC. After treatment with beta-glucuronidase to yield the aglycone, the separated fractions were hydrolysed to the corresponding benzophenones whose identity was confirmed by HPLC. Gas chromatography and gas chromatography-mass spectrometry demonstrated that the separated glucuronides corresponded to the enantiomeric benzodiazepines. Human urine and plasma as well as rabbit urine, plasma and bile were examined.

Benzodiazepines↗
PubMed1984

Determination of codeine in human plasma by reverse-phase high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method for the determination of codeine in human plasma is described. The specific, precise, and sensitive method can be used to determine plasma codeine levels after administration of therapeutic doses of codeine. After purification on a C18 extraction column, codeine in the form of hydrochloride is eluted. After addition of the internal standard, the codeine is separated on a reverse-phase C18 column using a slightly alkaline mobile phase and is then determined by UV detection. The analysis takes 3.5 min per run; the limit of detection is approximately 3 micrograms/L for a 50-microL loop and 800 microL of plasma. The absolute recovery is 98.4 +/- 6.7% (n = 14) in the 10-300-micrograms/L range. Within the range, the calibration curve is linear.

Adult↗
PubMed1982

The pharmacokinetics of valproic acid after oral and parenteral administration in healthy volunteers.

The pharmacokinetics of valproic acid were investigated in six healthy volunteers. After a single intravenous dose of 1,000 mg valproic acid, the pharmacokinetic parameters were determined according to the open two-compartment model. Bioavailability of valproic acid was performed comparing the areas under curves (AUC) after i.v and an equal single oral dose. The half-life of the initial phase was t 1/2 alpha = 0.64 +/- 0.32 h, and the elimination half-life was calculated as t 1/2 beta = 11.55 +/- 2.33 h. The distribution volume of the central compartment was Vc = 9.9 +/- 0.78 L, the apparent volume of distribution was Vd beta = 18.2 +/- 6.2 L, and the distribution volume at steady state was Vss = 12.6 +/- 1.2 L. The value for the average total clearance was Cltot = 51.1 +/- 11.9 ml/min. The study showed that in comparison to single dosing, the elimination half-life increased in average for four hours after multiple dosing (p less than or equal to 0.05). There was only a poor correlation between serum concentrations and concentration of valproic acid in saliva (r = 0.42).

Administration, Oral↗
PubMed1982

[5-Methoxypsoralen: bioavailability and pharmacokinetics].

The bioavailability of two galenic formulations of 5-methoxypsoralen (5-MOP) is described. A suspension in soft gelatine capsules was tested against a micronized powder in hard gelatine capsules on six volunteers, both in a dosage of 40 mg. The comparison of the AUC shows a significant better availability of the suspension (p less than or equal to 0.05). The detection limit of 5-MOP is 2 ng/ml plasma. The described analytical method is accurate and rapid--recovery near 100%--and is suitable for routine analysis. The pharmacokinetic parameters for 5-MOP are 2.3 h for the elimination half-life and 0.344 h-1 for the elimination rate constant.

5-Methoxypsoralen↗
PubMed1981

[Determination of benzbromarone in serum following combined therapy with allopurinol and benzbromarone (author's transl)].

A rapid method is described for benzbromarone assay in human serum. Protein precipitation is followed by extraction of the active substance. After centrifugation the clear organic layer is evaporated to dryness, redissolved in methanol and injected on a HPLC-column. Detection limits for this method of assay are 0.1 microgram benzbromarone/ml serum. The blood level for therapeutic concentrations lies between 1 and 2.5 microgram/ml. Some pharmacokinetic data were presented. The half-life of benzbromarone is 2.6 h.

Adult↗
PubMed1980

[A new and quick method for determination of allopurinol and oxipurinol in serum (author's transl)].

A method is described for allopurinol and oxipurinol assay in human serum for concentrations reached after usual therapy. The HPLC-method is based on a quick preparation of the serum samples including protein precipitation, evaporation to dryness, dissolving of the residue in citric acid and injecting the final solution on to the HPLC column. Detection limits for allopurinol are 0.05 microgram/ml serum and for oxipurinol 0.2 microgram/ml serum.

Allopurinol↗