Internally standardized method for the determination of nalbuphine in human plasma by means of high performance liquid chromatography with electrochemical coulometric detection.

A high performance liquid chromatographic method with internal analogue standardization and electrochemical detection for the determination of nalbuphine in human plasma is described. Using 3 ml plasma the lower limit of detection is below 50 pg/ml, during the routine assay the limit of determination can be fixed at about 250-300 pg/ml. The calibration curve is linear in the range between 0.163-65 ng/l, the recovery rate from plasma exceeds 80%. The method was successfully applied in several pharmacokinetic studies.

High-pressure liquid chromatographic method for the determination of hydromorphone in human plasma with electrochemical detection.

A high-pressure liquid chromatographic method with internal analogue standardization for the determination of hydromorphone (Dilaudid) in human plasma is described. The method involves extraction from plasma with chloroform and quantification with an electrochemical detector after high-pressure liquid chromatographic separation on an ion-pair column. Using 3 ml plasma the detection limit is about 50 pg/ml; in the routine procedure the limit of determination can be fixed at about 250 pg/ml with a correlation coefficient of about 10%. The method is selective. In case of extractions from blank plasma samples interfering peaks are not observed.

[Human pharmacokinetics of theophylline and etofylline from different formulations of a cardiotonic (author's transl)]. / Zur Humanpharmakokinetik von Theophyllin und Etofyllin aus verschiedenen Zubereitungen eines Kardiotonikums.

Serum concentrations of theophylline and etofylline were analysed by a specific HPLC-method in 6 volunteers after i.v. and p.o. administration of the cardiotonic Cordalin ampoules, drops and dragees. Maximum serum concentrations were reached by theophylline an etofylline at about the same time: 1.0-1.2 h after Cordalin drops; 2.3-2.6 h after Cordalin dragees. The half-life of serum elimination was 5.0-7.2 h for theophylline and 5.5-6.9 h for etofylline. The absolute bioavailability of the two oral formulations was calculated from the areas under the serum curves. For theophylline it is complete from the dragees and 78% from drops. Etofylline, too, is highly bioavailable: 94% from the dragees, 84% from drops. From the kinetic data the conclusion can be drawn that accumulation of theophylline and etofylline will be negligible after Cordalin if administered according to prescribed directions.

[Metabolism and pharmacokinetics of etofylline clofibrate, new antilipemic]. / Metabolismus und Pharmakokinetik von Etofyllinclofibrat, einem neuen Antilipmikum.

Upon investigations on metabolism and pharmacokinetics of 1-(theophyllin-7-yl)-ethyl-2-[2-(chlorophenoxy)-2-methylpropionate] (etofylline clofibrate, ML 1024, Duolip) is reported. As can be seen from in vivo tests in rats and dogs ML 1024 is cleaved to the metabolites clofibric acid and etofylline. This could be further demonstrated in vitro by incubation with lipases and human serum. The pharmacokinetic parameters of the metabolites after oral application of 2 capsules Duolip, corresponding to 500 mg etofylline clofibrate, were evaluated in 7 healthy volunteers. The serum fluctuations of the main metabolites could be adapted to an open two-compartment model (etofylline). The following mean values were found: the invasion half-life is 1 h 4 min for clofibric acid and 1 h 52 min for etofylline. The maximum concentration after approximately 4 h is 22.75 micrograms/ml for clofibric acid and 6.57 micrograms/ml for etofylline. The elimination half-life is 12.12 h for clofibric and 4.33 h for etofylline. Via urine 20 mg clofibric acid and 15.7 mg etofylline were excreted within 8 h. The elimination process after 8 h is not yet terminated.

[Relative bioavailability of a new spironolactone preparation (author's transl)]. / Relative Bioverfügbarkeit einer neuen Spironolacton-Zubereitung.

The investigations have been performed to determine the relative bioavailability of canrenon from Acelat 100 capsules in comparison with canrenon from a spironolactone standard preparation available on the German market. This was carried out by comparing the areas under the serum fluctuation curves after oral application of both preparations as well as by urine excretion extrapolated infinitely. The preparations were administered together with a standard breakfast. Subsequently up to 48 h blood was withdrawn from the Vena cubiti. According to a known method serum samples were analysed spectrophotometrically. The data obtained were fitted to an open two-compartment model with the RIP-procedure. The core of the program is a Gauss-Newton iteration (minimising the last squares). These are the results: By intraindividual comparison of the areas under the serum fluctuation curves of canrenon a relative bioavailability of 116.27% (s = 16.84) of canrenon from Acelat 100 could be calculated versus canrenon from the standard. Urine excretion, extrapolated infinitely, showed a 4% higher excretion of canrenon after application of Acelat 100 compared to standard. Both results are not significantly different in the range of biological scattering. The further pharmacokinetic parameters calculated were within the range of the literature available.

[Relative bioavailability of a vincamine retard formulation. Pharmacokinetic study in normal subjects (author's transl)]. / Relative Bioverfürgbarkeit einer Vincamin-Retard-Zubereitung. Pharmakokinetische Untersuchungen an gesunden Versuchspersonen.

The study was carried out in 6 healthy volunteers in cross-over design. The pharmacokinetic parameters were calculated after application of 60 mg vincamine base in comparison to a sustained release formulation (vincamine ratio-pharm 30 mg) on the basis of a GC method. Summarizing it can be stated that the sustained release formulation has a flatter profile and is therefore more adapted to clinical application. The extent of absorption expressed as AUC of the serum concentration-time curve, has three times the extent of the curve with the pure substance.