Assay method for product formation in in vitro enzyme kinetic studies of uridine diphosphate glucuronyltransferases: 2-arylpropionic acid enantiomers.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
H Spahn
Publications and source records attributed to H Spahn.
S-(+)-flunoxaprofen chloride as chiral fluorescent reagent.
Explore the source record for details and available documents.
Benzoxazoles↗
Simultaneous determination of R- and S-prenylamine in plasma and urine by reversed-phase high-performance liquid chromatography.
A high-performance liquid chromatographic method for the determination of R- and S-prenylamine in human plasma and urine is described. It involves a two-step liquid-liquid extraction of prenylamine from biological material and preparation of diastereomeric urea derivatives with R-(-)-naphthylethyl isocyanate, a chiral fluorescence marker. Separation and quantitation of the diastereomeric prenylamine derivatives are carried out by a reversed-phase high-performance liquid chromatographic system with fluorimetric detection. The limit of determination is less than 2 ng of enantiomer per ml of urine and less than 1 ng of enantiomer per ml of plasma. A preliminary kinetic study on one healthy volunteer who had received a single oral dose of racemic prenylamine (100-mg film tablet) showed distinctly higher plasma and urine concentrations of the R-enantiomer.
Administration, Oral↗
S-(+)-naproxen chloride as acylating agent for separating the enantiomers of chiral amines and alcohols.
Explore the source record for details and available documents.
Acylation↗
Plasma drug and antiplatelet profiles of the original acetylsalicylic acid preparations used in the AMIS, PARIS and German-Austrian trials for secondary prevention of myocardial infarction.
In a cross-over study 6 healthy male subjects were given for 9 days the acetylsalicylic acid (ASA) preparations used in the Aspirin Myocardial Infarction Study (AMIS), Persantine-Aspirin Reinfarction Study (PARIS) and German-Austrian secondary heart attack prevention trials, exactly according to the original study protocols. Plasma concentrations of ASA and its main metabolites salicylic acid (SA) and salicyluric acid (SUA), as well as platelet function (collagen-induced platelet aggregation; tissue extract-induced change in platelet shape) were studied repeatedly on the first day of each medication period and were again examined on the sixth and ninth days. Differences in the plasma concentrations of ASA and its metabolites were found only on the first day, probably as a result of different absorption rates. Collagen-induced platelet aggregation was more rapidly inhibited the faster the preparation was absorbed. Each ASA preparation inhibited tissue extract-induced platelet shape change from the first dose, although statistically significant inhibition was seen only with the AMIS preparation. It is concluded that differences in the antithrombotic efficiency of ASA cannot be explained by differences in the pharmacokinetic and antiplatelet profiles of the various ASA preparations tested.
Adult↗
Penbutolol: pharmacokinetics, effect on exercise tachycardia, and in vitro inhibition of radioligand binding.
The pharmacokinetics of penbutolol 40 mg, its reduction in exercise-induced tachycardia, and the in vitro inhibition of radioligand binding to beta-adrenoceptors by plasma have been investigated in 7 healthy volunteers. The peak penbutolol concentration of 285 ng/ml was observed 1.2 h after administration, and the maximum of 4'-OH-penbutolol of 4.76 ng/ml was found after 1.64 h. Penbutolol was detected for up to 48 h, and 4'-OH-penbutolol dropped below the limit of detection after about 10 h. The terminal plasma concentration of penbutolol declined with an average half-life of 19 h. The maximum reduction in exercise-induced tachycardia was 33 beats/min 2.6 h after taking penbutolol. There was still a significant reduction of about 7 beats/min after 48 h. This effect could be adequately explained by the concentration-time course of penbutolol in combination with Clark's model of the concentration-effect relationship. Antagonist activity in plasma caused 91% inhibition of radioligand binding in vitro to beta 2-adrenoceptors on rat reticulocyte membranes 1.6 h after intake of penbutolol. By 48 h after intake, radioligand binding was still significantly inhibited (23%). The in vitro inhibition of radioligand binding by plasma showed a linear correlation with the reduction in exercise-induced tachycardia for all phases of the workload. The time course of the reduction in heart rate was completely explained by the in vitro inhibition of radioligand binding. However, it was not possible to explain the in vitro inhibition of radioligand binding by the concentration-time course of penbutolol using a simple competition model, although both variables were based on the same sampling site. When the in vitro inhibition of radioligand binding was plotted against the penbutolol concentration at the same sampling times (with both variables transformed to multiples of the apparent inhibition constant) the discrepancy became even more apparent as time-related counterclockwise hysteresis. None of the known metabolites of penbutolol can explain the discrepancy between the penbutolol concentration and the inhibition of radioligand binding in vitro. It appears that an other active metabolite is formed, which contributes to the effect in vitro and in vivo and so can explain the observed discrepancy.
Adrenergic beta-Antagonists↗
Enantiospecific high-performance liquid chromatographic (HPLC) determination of baclofen and its fluoro analogue in biological material.
A method is described for the quantification of baclofen enantiomers in biological material (urine, plasma, and cerebrospinal fluid). The samples were extracted by liquid-solid extraction using Sep-Pak C18 cartridges. The subsequent derivatization procedure contained two separate steps. (1) The butyl esters of the enantiomers were formed using butanolic hydrochloric acid (followed by ion-pair extraction of the intermediate products). (2) A chiral derivatization was then performed using S-(+)-naproxen chloride as reagent. S-(+)-Benoxaprofen chloride can also be used. The diastereomeric amides were separated by high-performance liquid chromatography (HPLC) on a silica gel column (mobile phase, n-hexane/dichloromethane/ethanol; detection, fluorescence measurement at 335/365 nm). The described procedure was also used for the quantification of the fluoro analogue of baclofen. Urinary excretion of baclofen enantiomers was investigated in two healthy volunteers after p.o. administration.
Amides↗
Quantification of baclofen and its fluoro analogue in plasma and urine after fluorescent derivatisation with benoxaprofen chloride and thin-layer chromatographic separation.
An assay method for the quantification of the centrally acting muscle relaxant baclofen in human plasma and urine is described. Baclofen is separated from biological samples using Sep-Pak C18-cartridges. The liquid-solid extraction is followed by ion-pair extraction. The following procedure involves the formation of the baclofen butyl ester and an additional ion-pair extraction of the ester. Then a fluorescent derivatisation is performed, using the fluorescence marker benoxaprofen chloride. The resulting amide is separated from interfering compounds by TLC (silica gel) and quantified by directly measuring the fluorescence (313 nm/365 nm). The procedure described can also be applied for the determination of the fluoro analogue of baclofen. The lower limit of detection is 10 ng per 1 ml plasma and 20 ng per 0.1 ml urine. The applicability of the method was proved by investigating plasma and urine samples of 2 volunteers after oral administration of 20 mg baclofen as single dose.
Baclofen↗
Formation of diastereomeric derivatives of 2-arylpropionic acids using L-leucinamide.
Explore the source record for details and available documents.
Chemical Phenomena↗
Determination of metoprolol enantiomers in plasma and urine using (S)-(-)-phenylethyl isocyanate as a chiral reagent.
Explore the source record for details and available documents.
Chromatography, High Pressure Liquid↗
Rapid determination of the enantiomers of metoprolol, oxprenolol and propranolol in urine.
A method is described that makes possible the rapid determination of the enantiomers of beta-blocking agents. After extraction from urine samples (at pH 9.9) using toluene, the enantiomers are derivatised with S-(+)-benoxaprofen chloride. The chromatographic separation can be performed on thin-layer plates with toluene-acetone as mobile phase. The derivatives can be detected by measuring the fluorescence (lambda ex = 313 nm,lambda em = 365 nm).
Biotransformation↗
Pharmacokinetics of atenolol and metoprolol administered together with piroxicam.
Explore the source record for details and available documents.
Adult↗
Influence of cardiac function on the diuretic and hemodynamic effects of the loop diuretic piretanide.
The influence of cardiac function on the diuretic and hemodynamic effects of the loop diuretic piretanide was investigated in nine patients with congestive heart failure. The diuretic response to piretanide correlated significantly with the pretreatment cardiac index (r = 0.90). Furthermore, a significant correlation was found between the pretreatment fractional sodium excretion and the cardiac index (r = 0.85). The fractional sodium excretion is reciprocal to the renal sodium and water reabsorption. No change in the hemodynamics was observed prior to the onset of diuresis. At 120 minutes after administration of piretanide, the reduction of mean pulmonary capillary wedge pressure (r = 0.88) and mean right atrial pressure (r = 0.80) was significantly related to the diuretic response. We conclude that the reduced diuretic response to piretanide in patients with low cardiac index is due to increased renal sodium and water reabsorption. The hemodynamic changes following the administration of piretanide are dependent on the diuresis.
Adult↗
Pharmacokinetics of amiloride in renal and hepatic disease.
The pharmacokinetics of the antikaliuretic amiloride has been studied in healthy controls and in patients with chronic renal failure or hepatitis. It was 40% bound to protein. In healthy volunteers 49% of an oral dose was recovered unchanged in the urine. The renal clearance of amiloride was about 3 times the creatinine clearance, which means that it was predominantly excreted via tubular secretion. Renal impairment reduced the clearance of amiloride, causing a prolongation of the t1/2 and drug accumulation in plasma. In hepatitis the t1/2 of amiloride was prolonged and the AUC increased. Urinary recovery (Ae) of amiloride was greater in hepatitis patients than in controls.
Adult↗
Concentration of azapropazone in synovial tissues and fluid.
The concentration-time curves of azapropazone in synovial fluid and tissues have been studied in arthritic patients after an i.v. bolus (600 mg) and under steady-state conditions. Synovial fluid and tissue samples were taken intraoperatively 0.45-60 h after administration. The azapropazone concentrations in synovial fluid, synovial tissue and plasma were correlated. The levels in synovial fluid were usually lower than corresponding plasma levels. Under steady-state conditions azapropazone did not accumulate in synovial tissues.
Adolescent↗
Fluorimetric determination of levoprotiline in human plasma after thin-layer chromatographic or high performance liquid chromatographic separation.
The quantitative determination of the new antidepressant drug levoprotiline, the R-(-)-enantiomer of oxa-protiline (a-[methylamino)methyl)-9,10-ethanoanthracene-9(10H)-ethanol), in human biological material is described. Analysis is performed by alkaline extraction with n-heptane-isopropanol, subsequent fluorescence derivatisation with NBD chloride (4-chloro-7-nitrobenzofurazan), thin layer or high performance liquid chromatography, and fluorimetric measurement of the derivatisation product (lambda max ex. = 470 nm, lambda max em. = 525 nm). The sensitivity of the procedure (detection limit less than 1 ng/ml) permits the performance of pharmacokinetic studies after therapeutic doses.
Anthracenes↗
Pharmacokinetics and bioavailability of piretanide in healthy volunteers following intramuscular administration.
The pharmacokinetics of the diuretic compound 4-phenoxy-3-(1-pyrrolidinyl)-5-sulfamoylbenzoic acid (piretanide, Arelix) were investigated in 10 healthy male volunteers following intravenous and intramuscular administration of single doses of 6 mg. Plasma concentration-time data followed in general characteristics of a three-compartment model. Following intravenous administration, the terminal half-life of elimination was 1.29 +/- 0.40 h, the total clearance 219 +/- 36 ml/min and the steady state volume of distribution was calculated to be 12.4 +/- 2.1 l. The renal excretion of unchanged drug amounted to 34.4 +/- 6.9% of the dose. Following intramuscular administration, peak plasma concentrations of 366 +/- 85 mg/ml were achieved 13.8 +/- 4.8 min after administration. All other parameters were not statistically significantly different from those obtained after i.v. bolus. The bioavailability of piretanide following intramuscular administration was 0.88 +/- 0.17.
Adult↗
Determination of verapamil and norverapamil in human biological material. Investigation of plasma concentrations after oral administration of two different verapamil formulations.
A method for the simultaneous determination of the cardiovascular agent verapamil and its major metabolite norverapamil in human plasma is described. Analysis is performed after alkaline extraction with n-heptane by subsequent ion-paired high performance liquid chromatographic (HPLC) separation, and direct fluorimetric measurement of both compounds (lambda maxex. = 278 nm, lambda maxem. = 320 nm). The sensitivity of the procedure (detection limit less than 1 ng/ml) is suitable for pharmacokinetic studies after therapeutic doses. The applicability of the method was tested by performing a clinical study. Plasma concentrations of two verapamil formulations for oral administration were examined. The active metabolite norverapamil was included in the investigation.
Administration, Oral↗