PubMed Health⌕ Search

Biomedical subjects

V Rovei

Publications and source records attributed to V Rovei.

At least 37 records · Page 2Linked to original sources
PubMed1983

Plasma protein binding of the reversible type A MAO inhibitor cimoxatone (MD 780515).

Binding of a new selective reversible type A MAO inhibitor cimoxatone (MD 780515) to plasma proteins was studied in vitro by equilibrium dialysis. Binding to 580 microM human serum albumin (HSA) and to total plasma proteins was 93-96% and independent of cimoxatone concentration (0.15-207 microM). The drug was mainly bound to HSA with two binding sites and a moderate association constant (K = 2.9 X 10(4) M-1). Free fatty acids did not modify cimoxatone binding to HSA. Cimoxatone was also moderately bound to isolated lipoprotein fractions; alpha 1-acid glycoprotein and gamma-globulins did not play an important role in the binding of cimoxatone. MD 770222, the O-demethyl metabolite, appeared to be bound to HSA at the same binding sites as cimoxatone. However, no interaction occurred between the two compounds for 580 microM HSA. L-Tryptophan, bilirubin, the benzodiazepines flunitrazepam and oxazepam, imipramine and aspirin, did not displace cimoxatone from its binding sites. On the other hand, warfarin and phenylbutazone decreased cimoxatone binding to 29 microM HSA but no interaction occurred with 580 microM HSA.

Bilirubin↗
PubMed1983

Gas--liquid chromatographic determination of toloxatone in human plasma. Routine analysis of a wide range of drug concentrations using a nitrogen-selective detector.

A selective and sensitive gas--liquid chromatographic (GLC) method has been developed for the measurement of toloxatone at therapeutic concentrations in plasma. The technique is based on a single extraction from plasma at pH 10, the preparation of a trimethylsilyl derivative and detection by a nitrogen-selective detector. The traditional calibration curve, peak-area ratio of toloxatone to internal standard versus toloxatone plasma concentration, was slightly concave for the wide concentration considered (10-3000 ng/ml). As a consequence, the linear least-squares regression analysis gave a negative intercept on the gamma-axis which affected quantitation accuracy of low plasma concentration values. A calibration method taking into consideration the non-linearity of the calibration curve is proposed. The characteristics of the detector were examined in order to analyse response linearity and sensitivity. A linear relationship was found between background current and detector sensitivity.

Chromatography, Gas↗
PubMed1983

[Antidepressive action, pharmacokinetic characteristics and biochemical properties of cimoxatone, a new reversible MAO-A inhibitor].

Cimoxatone is a new monoamine oxidase inhibitor (MAOI) in comparison to the existing non-selective and irreversible MAOIs used in the therapy of depression. A clinical study has been carried out in 10 depressed patients. Cimoxatone was given from 0.32 to 0.78 mg/kg/day for 28 days. The drug was shown to be effective against depression and well tolerated at the given doses. The inhibition of monoamine oxidase and its reversibility were assessed by urinary excretion of 3-methoxy-4-hydroxy- phenylethyleneglycol sulphate. The treatment had no effect on the plasma prolactin levels. The plasma concentrations of cimoxatone reached a plateau after 3 to 4 days of therapy. The study confirmed earlier findings in healthy volunteers that the principal metabolite is also active as a type A MAOI. The plasma elimination of cimoxatone and its metabolite is almost complete 4 days after the last dosing.

Adult↗
PubMed1983

Bioavailability of Theodel, a new theophylline tablet, in humans.

The bioavailability of Theodel, a new scored tablet of theophylline, was investigated in eight healthy adult volunteers. Rate of absorption and AUC infinity were compared after single oral doses of Theodel (250 mg), of an aqueous solution (250 mg), and of two Theolair tablets (2 X 125 mg). Theophylline was rapidly absorbed from the Theodel tablet, with a t1/2abs of 0.44 +/- 0.37 h; maximum plasma concentrations of 8.0 +/- 2.3 mg/l were reached after 1.8 +/- 0.8 h. Almost the entire dose was recovered from urine as theophylline and its major metabolites, 1,3-dimethyluric acid, 1-methyluric acid, and 3-methylxanthine. Theophylline was, therefore, efficiently absorbed from this formulation. The plasma elimination half-life ranged from 5.9 to 10.4 h. Based on the assumption that absorption is complete, the plasma clearance ranged from 0.028 to 0.048 1 X h-1 X kg-1, and the apparent volume of distribution from 0.38 to 0.57 1/kg. No significant difference between the rate and the extent of theophylline absorption was observed for the three preparations, which are thus bioequivalent. Simulations of plasma levels after repeated administration of Theodel tablets showed that plasma theophylline concentrations remain in the therapeutic range with three doses per day.

Adult↗
PubMed1982

[Plasma level monitoring of psychotropic drugs in children. II -- Antidepressants (author's transl)].

Children and young adolescents with either depressive syndromes or enuresis were treated with clomipramine for periods of 1 to 9 months. Plasma concentrations of the drug and of its demethylated metabolite were monitored and compared with clinical effects. In children, clomipramine proved rapidly absorbed by the oral route, and its rate of distribution seemed to be related to age since the dose-concentration ratio was lower in the youngest subjects. There was a clear correlation between side-effects and clomipramine levels but not demethyl-chlorimipramine levels. In enuresis, a therapeutic effect was obtained with clomipramine levels of 20 to 60 ng/ml; lower levels were associated with ineffectiveness and higher levels with side-effects. The relationship between daily doses and plasma concentrations varied considerably from one patient to another but was almost constant in the same individual. The results obtained underline the usefulness of routinely monitoring antidepressant plasma levels in children.

Adolescent↗
PubMed1982

Pharmacokinetics of theophylline: a dose-range study.

1 Pharmacokinetics of theophylline were investigated in a group of healthy adult volunteers (non smokers and on xanthine-free diet) following single oral administration of 125, 250, 375 and 500 mg doses as tablets (Theodel). 2 Absorption of theophylline was rapid and followed first-order kinetics. Plasma curves were fitted according to a one compartment open model. 3 There was a linear relationship (P less than 0.001) between plasma Cmax or AUCx values and the administered dose. The analysis of variance showed that the pharmacokinetic parameters of theophylline (t1/2 abs, tmax, t1/2 beta, CL, CLR, Vd and F) were not modified at any dose. 4 Absorption of the drug was complete since the recovery in urine of theophylline (13.7 to 16.8% of the dose) and its major metabolites, 1,3-dimethyluric acid (35 to 42%), 1-methyluric acid (21.3 to 26.7%) and 3-methylxanthine (11.5 to 13.7%), accounted for the administered dose. Some impairment of demethylation to 3-methylxanthine was observed in two subjects, however the percentage of theophylline and its major metabolites excreted in urine was constant for all the four doses. 5 On the basis of these results, after single oral administration, elimination of theophylline followed first-order kinetics in the range of doses investigated (1.62 to 10.42 mg/kg).

Adult↗
PubMed1982

Pharmacokinetics of toloxatone in man following intravenous and oral administrations.

Pharmacokinetics of the antidepressant drug toloxatone were investigated in man following intravenous and oral administration. Five healthy adult volunteers received a single 1 mg/kg dose given as a gelatin capsule (p.o.) and an i.v. infusion. After p.o. administration toloxatone was rapidly absorbed, peak plasma concentrations (Cmax) ranging from 0.384 to 0.640 mg/l occurred between 0.53 and 1.00 h. Plasma curves were fitted according to a one-compartment open model. After absorption, toloxatone was cleared from plasma with a half-life (t 1/2 beta) of 0.96-1.81 h. Following i.v. administration Cmax values from 0.623 to 0.840 mg/l were reached at the end of the 0.5-h infusion. As observed for the capsule form, the elimination of the drug from the plasma was monophasic with t 1/2 beta of 0.88-2.46 h. Plasma clearance of toloxatone was high (0.462 to 0.860 l/h . kg) and the apparent volume of distribution ranged between 1.09 and 1.64 l/kg. Protein binding to plasma proteins is near 50% and appears almost exclusively due to albumin. Free fatty acids do not modify substantially the degree of binding which is constant over the range of concentrations from 0.05 to 100 mg/l. The availability of the gelatin capsule was 50-62% of the i.v. infusion. Since toloxatone is extensively eliminated in urine as metabolites, the reduced availability of the drug appears to be related mainly to first pass metabolism.

Administration, Oral↗
PubMed1981

Quantitative determination of naproxen in plasma by a simple high-performance liquid chromatographic method.

A high-performance liquid chromatographic method for the determination of naproxen in plasma is described. The technique is based on the single extraction of the drug from acidified plasma with chloroform using 2-naphthalene acetic acid as internal standard. The chromatographic system consisted of a column packed with Spherisorb ODS (5 micrometer); the mobile phase was acetonitrile--phosphoric acid (pH 3) (45:55, v/v). The method can accurately measure plasma naproxen concentrations down to 1 microgram/ml using 100 microliter of sample, with no interference from endogenous compounds. The coefficients of variation of the method at 120 microgram/ml and 1 microgram/ml are 2.8 and 21.6%, respectively, and the calibration curve is linear. The method described is very suitable for routine clinical and pharmacokinetic studies.

Anti-Inflammatory Agents↗
PubMed1981

Determination of antrafenine and its main acid metabolite, 2-{[7-(trifluoromethyl)-4-quinolinyl]amino}-benzoic acid, in biological fluids using high-performance liquid chromatography with large volume automatic injection and gas-liquid chromatography with derivative formation.

Specific and sensitive analytical methods have been developed for the measurement of antrafenine and its main acid metabolite, 2-([17-(trifluoromethyl)-4-quinolinyl] amino) benzoic acid (FQB), at therapeutic concentrations in plasma and urine. Following the addition of internal standards (the methyl ester of FQB and 2-([8-(trifluoromethyl)-4-quinolinyl] amino) benzoic acid) the parent drug and the metabolite were extracted from biological material with diethyl ether at a weakly acid pH. Drug extracts were evaporated to dryness prior to chromatographic analysis. Antrafenine was measured by high-performance liquid chromatography using a Spherisorb 5-micrometer ODS column with acetonitrile-0.1 M sodium acetate as the mobile phase. Samples were injected automatically using a 500-microliter injection loop. The detector wavelength was 353 nm corresponding to the maximum UV absorption of both drug and internal standard. The coefficient of variation (C.V.) for the determination of antrafenine concentrations between 5 and 250 ng/ml ranged between 24 and 3%, respectively. The acid metabolite of antrafenine was measured by gas-liquid chromatography with electron-capture detection using a 1 m column packed with 3% OV-225 on Gas-Chrom Q (100-120 mesh) at 240 degrees C and on-column methylation with trimethylphenyl ammonium hydroxide. The C. V. of the method for the analysis of metabolite concentrations between 10 and 500 ng/ml ranged between 3 and 9%, respectively.

Aminoquinolines↗
PubMed1980

Analysis of tricyclic antidepressant drugs by gas chromatography using nitrogen-selective detection with packed and capillary columns.

A gas chromatographic method using either a conventional packed column (3% SP-2250) or a capillary column (SE-30) for the measurement of therapeutic plasma concentrations of tricyclic antidepressant drugs and their demethylated metabolites is described. The technique is based on a simple hexane extraction of drugs from alkalinized plasma followed by derivatization with heptafluorobutyric anhydride for the measurement of demethylated compounds. Subsequently, parent drugs and derivatives are chromatographed and detected using a nitrogen-selective detector. A comparison of the results using both types of chromatographic systems is discussed.

Antidepressive Agents, Tricyclic↗
PubMed1980

Comparison of single-dose pharmacokinetics of imipramine and maprotiline in the elderly.

Pharmacokinetic profiles of imipramine and a newer tetracyclic antidepressant, maprotiline, were studied in elderly (75-83 years of age) subjects who were given a single oral dose of 125 and 175 mg, respectively, of these drugs. The apparent elimination half-life of imipramine was 20.8-34.9h (means 26.4h), its biovailability (F) was 40-64% (means 57%), and the apparent plasma clearance was from 0.27-0.57h/kg (mean 0.41h/kg). Maprotiline had a longer half-life (mean 31.5h range 20.6-51.8h, but its bioavailability (mean 50%) and plasma clearance (mean 0.49h/kg) values were in the range similar to those seen after imipramine. It appears that the elimination half-life of imipramine is longer and its plasma clearance is markedly reduced in elderly subjects when compared to values reported in young adults. Subjective clinical side effects were minimal with the two drugs. However, alterations in heart rate, blood pressure, or electrocardiogram occurred in all subjects. This suggests that caution should be exercised before initiating and during the treatment of elderly patients with these antidepressant drugs.

Aged↗
PubMed1980

Simple and specific high performance liquid chromatographic method for the routine monitoring of clonazepam in plasma.

A simple, specific, and sensitive high performance liquid chromatographic (HPLC) method for the determination of clonazepam in plasma is described. The drug was extracted with chloroform at an alkaline pH using flunitrazepam as internal standard. The HPLC analysis was performed using a column packed with Spherisorb C6 reverse phase, the mobile phase being a solution of acetonitrile sodium acetate 0.1 M (40/60, v/v); the ultraviolet detector was set at 306 nm. The calibration curve was linear for plasma concentrations between 2 and 200 ng/ml-1 when 1 ml of sample was analyzed. Diazepam, its metabolites, and the most common antiepileptics did not interfere with the analysis. The coefficient of variation at the lowest concentration was 14%. With this method, clonazepam can also be used as internal standard for the determination of flunitrazepam. The performance of the column was still satisfactory after the analysis of more than 500 plasma samples.

Adult↗
PubMed1980

Long-term monitoring of tricyclic antidepressant plasma concentrations.

Plasma levels of antidepressant drugs were measured in 17 depressed patients at roughly monthly intervals over follow-up periods of three to 26 months. Good results in seven were associated with small fluctuations in level from visit to visit, while big fluctuations were associated with poor outcome. Such fluctuations were probably from poor compliance or drug interaction from self-medication. Severe side effects and cardiotoxicity were associated with high levels.

Adult↗
PubMed1980

Pharmacokinetics and metabolism of diltiazem in man.

Dilitazem, a coronary vasodilating agent, after oral administration of four different doses, was well and rapidly absorbed. The pharmacokinetics of the drug followed a two-compartment model, with a rapid distribution and an elimination with a half-life of 4-7 hours. After chronic treatment the pharmacokinetic parameters were practically unchanged and therefore no accumulation of the drug was observed. The comparison between capsule and tablet preparations showed that both forms had a similar bioavailability. Diltiazem was extensively metabilized and only a few percent of the drug was found in urine. Several metabolites, also present as conjugates, have been identified by means of gas chromatography-mass spectrometry.

Administration, Oral↗