Fluorimetric determination of fluvoxamine or clovoxamine in human plasma after thin-layer chromatographic or high-performance liquid chromatographic separation.
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Antidepressive Agents↗
Biomedical subjects
H Spahn
Publications and source records attributed to H Spahn.
The development of reliable compliance tests for antihypertensive drugs.
Many tests for measuring compliance have been proposed, but in most cases compliance rates have been determined without taking into account the factors influencing the interval during which a drug can be detected by a qualitative test after having been taken by the patient. The drug half-life, often used for determining the time at which the sample is collected, is inadequate for obtaining conclusive test results. A procedure is described for the determination of urine collection intervals during which reliable information on compliance can be obtained, using oxprenolol, hydrochlorothiazide, and pindolol as examples.
Antihypertensive Agents↗
Penbutolol Pharmacokinetics: the influence of concomitant administration of cimetidine.
A possible interaction of penbutolol and cimetidine was investigated in healthy volunteers treated orally for 7 days. The plasma levels of unmetabolized penbutolol showed a slight but non-significant increase. The biphasic elimination kinetics of penbutolol (half-lives 0.8 and 17 h) was not affected by coadministration of cimetidine. Plasma levels of penbutolol were not significantly altered by chronic treatment with cimetidine, whereas the levels of 4-hydroxypenbutolol and 4-hydroxypenbutolol glucuronide were significantly reduced.
Adult↗
Controlled trial on the possible advantages of a combined therapy with maprotiline and haloperidol in endogenous depression.
There is some clinical evidence that neuroleptics are able to increase the therapeutic effect of antidepressant drugs. From a theoretical viewpoint this could be due to influences on pharmacokinetics or receptor sensitivity. In a controlled three-week trial in 28 patients with endogenous depression the potential advantages of a combined medication of 150 mg maprotiline and 9 mg haloperidol per day (given for the first six days) in comparison with monotherapy with maprotiline were tested. Neither during the time of combined medication nor following withdrawal of haloperidol did this treatment regimen show better clinical results in comparison with controls. In keeping with results described elsewhere, the serum levels of the antidepressant, but not of its desmethyl metabolite, were higher in the experimental group.
Adult↗
An approach to reduce the number of skin samples in testing the transdermal permeation of drugs.
Although glyceryl trinitrate (GT) is a drug that easily permeates through skin, the variations in its transepidermal fluxes were high. The arithmetic mean of the GT flux (n = 31 skin samples from different individuals) was 16.5 micrograms cm-2 h-1 with a standard deviation of 42%. The extreme values were 4.1 and 36.9 micrograms cm-2 h-1, i.e. they differed by a factor of 9. Wide variations were also found for ephedrine, frusemide, caffeine, ethacrynic and benzoic acids and especially trospium chloride. All these fluxes were determined in an in-vitro permeation model at 32 degrees C using human epidermis. With the aim of standardizing epidermal preparations on their permeability, the extent to which the in-vitro GT fluxes through a human epidermal preparation correlate with those of other compounds was evaluated. The resulting standardization procedure consisted of two interactive parts: the correlation of the flux of a test-substance with that of GT using epidermal samples from three donors and estimating the minimum, mean and maximum flux of the test compound and quantitation of the transepidermal permeation of the test compound with those standardized epidermal preparations by calculating the GT standard coefficient defined by the slope of the line derived from the relation between GT flux units and the corresponding flux from the test compound.
Female↗
Determination of the bioavailability of the quaternary compound trospium chloride in man from urinary excretion data.
For the quaternary compound trospium chloride (Spasmex) which is used as an anticholinergic agent a new sensitive assay method has been developed that allows the quantitative determination of the drug in human urine and plasma. Using this method it was possible to obtain pharmacokinetic data from plasma levels and urinary excretion, and to determine the bioavailability in man. Quantitative determination is performed by alkaline hydrolysis to the corresponding spiroalcohol, ion-pair extraction with dipicrylamine, subsequent derivatization with the fluorophor benoxaprofen chloride, and ion-pair chromatographic separation on a reversed-phase column with chloride as the counter-ion using a mixture of acetonitrile and water. In healthy volunteers (n = 6) the plasma concentration time curve after intravenous administration of 0.5 mg trospium chloride could be described by an open two-compartment model. The mean half-lives were 2.7 and 97 min, respectively. After oral administration of 10 mg the highest concentration found in plasma was 1.4 ng trospium chloride/ml. 55% of the given dose were excreted unchanged into urine within 48 h after i.v. administration, the corresponding value after oral administration was 1.6%. If no hydrolysis is carried out in urine samples the spiroalcohol can be detected as metabolite of trospium. Within 48 h after i.v. administration 4% and after oral administration 0.3% of the given dose are excreted into urine as spiroalcohol. From the cumulative excretion of trospium into urine within 48 h a mean bioavailability of 2.9% was calculated.
Administration, Oral↗
Pharmacokinetics of salicylates administered with metoprolol.
The widely used acetylsalicylic acid (ASA, Colfarit) was administered in combination with metoprolol (Lopresor) during 7 days. Plasma concentrations of total salicylates (ASA and salicylic acid (SA) and metoprolol were monitored during the treatment period, on day 7 urinary excretion was also investigated. The kinetic data of the compounds were compared to those of the metoprolol and ASA control periods. Metoprolol kinetics remained uninfluenced whereas the maximal plasma concentrations of the salicylates were significantly higher than in the ASA control period.
Adult↗
Fluorimetric determination of the quaternary compound trospium and its metabolite in biological material after derivatization with benoxaprofen chloride.
The quantitative determination of the quaternary compound trospium and the corresponding spiroalcohol is described for human biological material. Analysis is performed by alkaline hydrolysis, ion-pair extraction into chloroform, subsequent derivatization with the flurophor benoxaprofen chloride and high-performance liquid chromatographic separation on a reversed-phase column. The limit of quantitation is ca. 1 pmol (1.03 pmol=lng of trospium chloride) per millilitre of plasma.
Benzilates↗
Determination of pindolol in plasma and urine by thin-layer chromatography.
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Chromatography, Thin Layer↗
Plasma salicylate levels and platelet function after acute and chronic administration of slow-release acetylsalicylic acid (Monobeltin).
The relationships between the antiplatelet effects and the pharmacokinetics of a slow release formulation of acetylsalicylic acid (ASA) have been investigated. After acute intake of 750 mg ASA in a slow-release formulation (Monobeltin), a slow increase in plasma ASA was paralleled by a gradual decrease in certain platelet functions. During chronic medication (750 mg twice daily), ASA was present in plasma at all times accompanied by full inhibition of platelet aggregation. For chronic antiplatelet therapy, this slow release formulation of ASA appears to be very effective, unless rapid inhibition of platelet function must be achieved.
Adult↗
[The bioavailability of combination preparations of acetylsalicylic acid and codeine phosphate].
Plasma levels time curves of acetylsalicylic acid, salicylic acid, salicyluric acid and codeine were monitored after intravenous, oral and rectal application (single dose) of preparations containing acetylsalicylic acid and codeine. The mean absolute bioavailability of acetylsalicylic acid was 68% after oral application and 60% after rectal application. The corresponding bioavailability data of codeine were 59% and 63%, respectively.
Administration, Oral↗
The influence of aluminium hydroxide on the bioavailability of feprazone. Single dose study.
The influence of aluminium hydroxide (given as a suspension, Aludrox) on the oral bioavailability of feprazone was tested. The degree and speed of absorption of feprazone from capsules (400 mg feprazone as a single dose; 8 volunteers) was investigated by determining plasma levels of feprazone and one of its metabolites using an HPLC method. No statistically significant change in feprazone kinetics caused by the antacid was evident. Cmax (means +/- SEM) decreased from 40.6 +/- 2.9 to 36.25 +/- 1.4 micrograms/ml; the mean area under the plasma level time curve was somewhat higher after additional administration of aluminium hydroxide (n. s.).
Adult↗
alpha-Alkyl-alpha-arylacetic acid derivatives as fluorescence markers for thin-layer chromatographic and high-performance liquid chromatographic assay of amines and alcohols.
Activated R,S-benoxaprofen is described as a new reagent for fluorescent derivatization of drugs with primary or secondary amino groups or with hydroxyl groups. Separation of the reaction products is demonstrated by thin-layer chromatography and high-performance liquid chromatography. The sensitivity of the detection is in the picomole range. Derivatization procedures can be easily and rapidly performed.
Air↗
Activated alpha-alkyl-alpha-arylacetic acid enantiomers for stereoselective thin-layer chromatographic and high-performance liquid chromatographic determination of chiral amines.
The separation of racemic benoxaprofen into the two benoxaprofen enantiomers by preparative high-performance liquid chromatography and the application of the activated enantiomers as derivatization reagents for the simultaneous stereoselective determination of chiral amines in biological material is described. Activated (+)- and (-)-benoxaprofen are both shown to be very sensitive and stable chiral fluorescence markers, applicable to thin-layer chromatography as well as to high-performance liquid chromatography.
Amines↗
The interaction between H2-receptor antagonists and beta-adrenoceptor blockers.
The degrees of interactions between the H2-receptor antagonists, cimetidine and ranitidine, and several beta-adrenoceptor blockers were investigated in healthy volunteers following 7 days of oral monotherapy with penbutolol, propranolol, metoprolol, pindolol and atenolol, and after co-administration with each of the H2-receptor antagonists. The kinetic parameters of unmetabolised penbutolol and penbutolol glucuronide were unaffected, whereas the levels of 4-hydroxypenbutolol and 4-hydroxypenbutolol glucuronide were significantly reduced. Furthermore, cimetidine led to a marked increase in propranolol and metoprolol plasma levels. During co-administration with cimetidine, pindolol plasma levels were only slightly raised, whereas the pharmacokinetics of atenolol were not affected. With regard to pharmacodynamics, the inhibition of exercise-induced tachycardia by each of the beta-adrenoceptor blockers was not affected by cimetidine. Ranitidine did not alter atenolol plasma levels, but did raise the peak plasma concentration of metoprolol by about 30%. It is concluded that cimetidine interactions do occur and can be predicted for substances metabolised by the cytochrome P-450 pathway.
Adrenergic beta-Antagonists↗
Interaction between the beta-adrenoceptor blockers metoprolol and atenolol with amitriptyline and their effects on oxidative liver metabolism.
Neither the kinetics of the hydrophilic beta-adrenoceptor blocker atenolol nor those of the lipophilic metoprolol were influenced by the concurrent administration of amitriptyline. Compared with placebo, chronic administration (14 days) of atenolol and metoprolol (each as monotherapy) did not significantly reduce oxidative liver metabolism as measured by antipyrine half-life and by 6-beta-hydroxycortisol excretion. Compared with atenolol and metoprolol monotherapy, chronic administration of amitriptyline concurrently with each of the beta-adrenoceptor blockers produced an insignificant decrease (circa 10-20%) in antipyrine half-life and 6-beta-hydroxycortisol excretion. Amitriptyline appears therefore to have little enzyme-inducing activity.
Adult↗
Pharmacokinetic and pharmacodynamic interactions between phenprocoumon and atenolol or metoprolol.
Pharmacological interactions in both directions between phenprocoumon and atenolol and metoprolol were investigated using a crossover trial. Co-administration of phenprocoumon did not significantly affect Cmax, tmax, t1/2,22, AUC for atenolol or metoprolol. Co-administration of metoprolol, but not atenolol, increased mean plasma phenprocoumon concentrations 4 and 6 h after dosing and was caused by a decrease in the apparent volume of distribution. This increase in plasma phenprocoumon was not associated with an increase in prothrombin time or in the total area under the concentration-time curve. Although the transient increase of phenprocoumon plasma levels caused by metoprolol may be of little clinical significance after a single dose of phenprocoumon, a more important alteration in phenprocoumon disposition and effect should be considered in individual patients on long-term therapy.
4-Hydroxycoumarins↗
Influence of ranitidine on plasma metoprolol concentrations.
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Drug Interactions↗