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Biomedical subjects

H Blume

Publications and source records attributed to H Blume.

At least 55 records · Page 3Linked to original sources
PubMed1993

[Biological availability of gastric juice-resistant coated diclofenac preparations. 1. Bioavailability study following a single administration of a multiple-unit formulation in comparison with a single-unit formulation].

Bioavailability Study of Enteric Coated Diclofenac Formulations/1st Communication: Bioavailability study following single-dose administration of a multiple-unit formulation compared with a single-unit formulation Relative bioavailability of diclofenac (CAS 15307-86-5) was investigated after single-dose administration of an enteric coated multiple-unit formulation (Diclo-Puren 50, test) in comparison to a single-unit dosage form (reference). The study was carried out in a three-way changeover design with a group of 18 healthy male volunteers. Diclofenac plasma concentrations were measured using a selective and sensitive GLC-MS method after liquid-liquid extraction and subsequent derivatisation. Area under the curve (AUC) and maximum plasma concentrations (Cmax) were evaluated as pharmacokinetic characteristics. Moreover, time of maximum plasma concentration (tmax), lag-time (tlag) and plateau time of concentrations above minimum effective concentrations (MEC) of 50 ng/ml (tMEC(50)) and 100 ng/ml (tMEC(100)), respectively were calculated. Bioequivalence concerning AUC and Cmax was assessed by calculating 90%-confidence intervals using parametric (ANOVA, ANOVAlog) and non-parametric (Mann-Whitney) methods. Due to the inclusion rule bioequivalence was accepted if one of the calculated intervals was completely in the range of 80 to 125% (AUC) and 70 to 143% (Cmax). tmax, tlag and tMEC were evaluated considering the differences of mean values. Individual plasma profiles of diclofenac are more homogeneous after administration of the test formulation than after administration of the reference product. Mean relative bioavailability of the test formulation was calculated as 99%. Maximum plasma concentrations (mean +/- SD) were determined as 1159 +/- 632 ng/ml (test) and as 1481 +/- 637 ng/ml (reference). Maximum plasma concentrations (mean +/- SD) occurred 1.4 +/- 0.7 h (test) and 1.8 +/- 0.7 h (reference) after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Development of an HPLC method for determination of chloroquine in plasma].

A simple, rapid and sensitive ion-pair high-performance liquid chromatographic method is described, which allows the quantification of chloroquine in human plasma. 7-Chloro-4-(4-ethylpropylamino-1-methyl-butylamino)quinoline was synthesized and used as internal standard. After extraction by toluene from 1 ml plasma, chloroquine was reextracted with 15% phosphoric acid from the organic phase. Chromatographic separation on a RP-18 column and UV-detection (343 nm) allows sensitive determination of chloroquine in plasma with a lower limit of quantification of 2.5 ng/ml. The method was successfully applied to human plasma samples from 16 subjects after oral administration of 250 mg chloroquine diphosphate.

Chloroquine↗
PubMed1993

Plasma concentrations of S-verapamil after single doses of two different galenic formulations of racemic verapamil.

The results of enantioselective analysis of verapamil (CAS 52-53-9) in plasma samples obtained at tmax after single dose applications of a 80 mg fast dissoluting (IR) tablet, a controlled release (CR) formulation (240 mg) and an intravenous injection of 5 mg verapamil are reported. The mean fraction of S-verapamil obtained in samples containing the Cmax of racemic verapamil was somewhat smaller after application of the IR-form than observed with the CR formulation. (IR = 15.8 +/- 3.8%; CR = 18.8 +/- 2.0%; p < 0.01), after the intravenous application the mean S-fraction was 32.8 +/- 1.4%. In vitro dissolution tests of the two oral preparations prove that the isomers were released as racemate.

Administration, Oral↗
PubMed1992

Bioavailability study of two different verapamil formulations.

Relative bioavailability and bioequivalence of two oral verapamil preparations were investigated (dosage 80 mg, film-coated tablets as reference, dragées as test formulation). The clinical study was performed in a 2-period-cross-over design with 16 male healthy volunteers (mean age 28.8 +/- 3 years). The active metabolite norverapamil was included in the investigation. To assess bioequivalence several pharmacokinetic characteristics (i.e. AUC(o-oo), Cmax, tmax) were taken into account. Shortest 90% confidence intervals were calculated based on parametric (ANOVA, ANOVAlog) and non-parametric (Wilcoxon, Mann-Whitney) statistical tests. A positive decision for bioequivalence was accepted if the confidence intervals did not exceed the limits of 80-120% for AUC and 70-130% for Cmax. A mean relative bioavailability of 127% for the test preparation was found. Thus, bioavailability of the dragées is marked higher than bioavailability of the film-coated tablets.

Adult↗
PubMed1992

Chest imaging within the radiology department by means of photostimulable phosphor computed radiography: a review.

Photostimulable phosphor computed radiography has been clinically used outside of Japan for more than 8 years. Results of at least 35 quantitative or semiquantitative studies have been published so far in which the clinical utility of computed radiography (CR) is compared with that of conventional screen/film radiography (FR) for the study of the adult chest within the radiology department. The results can be summarized as follows: CR is superior to FR in the mediastinum, retrocardiac region, and subdiaphragmatic recesses, as well as in the evaluation of coronary artery calcifications. CR is reported to be generally superior or equivalent in the detection and evaluation of pulmonary nodules and larger pulmonary opacities. Equivocal results have been reported for pathologies requiring the inspection of fine details, such as interstitial infiltrates or pneumothorax. The studies indicate that image processing algorithms dedicated to the delineation of specific anatomies or pathologies improve clinical performance.

Coronary Angiography↗
PubMed1992

Concentration/effect relationship and enantioselective analysis of verapamil in hypertensive patients.

The concentration/effect relationship of verapamil was analyzed in 9 hypertensive patients using concentrations of racemic verapamil and the corresponding decrease in mean arterial blood pressure (MBP) in a sigmoidal Emax model. Concentration/effect data were obtained after a first dose (240 mg sustained release preparation) and at steady state after stepwise dose adjustment to obtain satisfactory BP control (less than 90/150 mm Hg). Emax (MBP) ranged from 15 to 40 mm Hg, and EC50 averaged 81 +/- 40 ng/ml (mean +/- SD). The fraction of S-verapamil in the overall racemic verapamil concentrations was measured in two patients by chiral high-performance liquid chromatography (HPLC) and showed a slight increase at steady state from 12.2 +/- 1.5 to 14.4 +/- 1.4% and from 14.0 +/- 1.3 to 16.3 +/- 0.6%. Concentration/effect curves for S-verapamil concentrations were similar to those obtained with racemic verapamil concentrations.

Administration, Oral↗
PubMed1992

Bioequivalence studies: single vs multiple dose.

Bioequivalence of different preparations of the same drug substance has gained considerable importance over the last few years due to increasing generic substitution. The procedure that the manufacturer of the generic test preparation has to show bioequivalence with an appropriate reference preparation is scientifically accepted and laid down in international regulations. However, the necessity of single- vs multiple-dose bioequivalence studies has not been discussed in detail with the exception of the Dutch and US guidelines on sustained-release theophylline formulations, where multiple-dose studies are specifically required. This paper compares the conclusions drawn from single- and multiple-dose studies in the same subjects and recommends appropriate pharmacokinetic characteristics.

Chemistry, Pharmaceutical↗
PubMed1991

Clinical chronopharmacology of oral sustained-release isosorbide-5-mononitrate in healthy subjects.

In 10 healthy male subjects the pharmacokinetics and haemodynamic effects of sustained-release isosorbide-5-mononitrate 60 mg (IS-5-MN) were studied after oral administration at two different times in the day (08.00 h and 20.00 h). Effects on blood pressure and heart rate after 3 min standing upright were measured in relation to the individual circadian control values. The pharmacokinetic parameters (Cmax, tmax, AUC, t 1/2) did not differ after morning and after evening dosing, tmax being 5.2 h and 4.9 h, respectively. In contrast, the cardiovascular effects of IS-5-MN were clearly circadian phase-dependent. The maximum decrease in blood pressure decrease and increase in heart rate occurred significantly earlier after the evening (BPsys 2.8 h; BPdia 2.9 h; HR 3.8 h) than after the morning dose (BPsys 5.0 h; BPdia 6.0 h; HR 5.2 h). Thus, the peak haemodynamic effects coincided with the peak drug concentration after the morning dose, whereas the peak effect was in advance of the peak drug concentration after the evening dose of IS-5-MN. The data provide evidence of circadian phase-dependency in the dose-response relationship of oral IS-5-MN.

Administration, Oral↗
PubMed1991

Right hemisphere advantage for evaluating emotional facial expressions.

The ability to evaluate the intensity of emotional facial expressions was investigated in patients undergoing the intracarotid sodium amytal procedure. It was found that when the hemisphere non-dominant for language (usually right) was anesthetized, the patients' ratings of the intensity of emotional expressions in photographs were lower than baseline ratings of these expressions. Such an effect was not seen with anesthetization of the hemisphere dominant for language (usually left). Ratings of shades of gray (which served as control stimuli) showed no such effect. The findings are interpreted in terms of a right hemisphere superiority in the perception and evaluation of emotional expression.

Adolescent↗
PubMed1991

Pharmacodynamic profile of verapamil in relation to absolute bioavailability: investigations with a conventional and a controlled-release formulation.

The absolute bioavailability F and response (prolongation of the PR interval) of verapamil after single doses of the same oral formulation administered on two different days were investigated in 16 male subjects with an 80 mg fast dissolving and a 240 mg controlled-release preparation and compared with a bolus injection of 5 mg of verapamil. The absolute bioavailability was 23% in both investigations for the 80 mg preparation and 32% in both investigations for the 240 mg dosage form. The individual values obtained for tmax, cmax, F, and AUC0-alpha showed a wide intersubject variability; therefore, no significant differences could be observed between the two trials for each dosage, but significant differences existed between the investigations of the two preparations. After intravenous administration, concentration-effect curves were about twofold left shifted when compared with the 80 mg tablet and about threefold left shifted when compared with the 240 mg tablet. Estimation of the drug input rate showed significantly (p less than 0.05) smaller values when the controlled-release tablet was given (80 mg tablet: 95.1 and 107.7 mg/h; 240 mg tablet; 55.8 and 46.3 mg/h). Thus, the effect and bioavailability of verapamil show sufficient intersubject reproducibility if the same formulation is given. The differences between the responses and the bioavailability after administration of different preparations may be related as well to the drug absorption rate and the stereoselective first pass of verapamil as to saturation of first-pass metabolism.

Administration, Oral↗
PubMed1991

[Bioavailability and bioequivalence of organic nitrates. Isosorbide dinitrate--a study of sustained-release preparations].

Assessment of Bioavailability of Organic Nitrates/Comparative bioavailability study of sustained-release isosorbide dinitrate preparations. Relative bioavailabilities of isosorbide dinitrate (ISDN, CAS 87-33-2) and the metabolite isosorbide-5-mononitrate (IS-5-MN, CAS 16051-77-7) were studied after application of Maycor retard 40 (sustained-release capsules, multiple unit formulation, test preparation) in comparison to sustained-release tablets (single unit formulation, reference preparation) with 16 healthy male volunteers in a two-way crossover design. Test and reference formulations were previously characterised in vitro by dissolution tests. ISDN, IS-5-MN (IS-2-MN) plasma concentrations were determined using a selective and sensitive GLC-method with ECD-detection. As pharmacokinetic parameters AUC, Cmax and half value duration (HVD) were evaluated. Bioequivalence was assessed by calculating 90%-confidence intervals (ANOVA, ANOVAlog, Mann-Whitney-test) for ISDN and IS-5-MN. Bioequivalence was accepted if due to the inclusion rule one of the calculated intervals fulfill the requirements of 80 and 120% (AUC) or 70 and 130% (Cmax, HVD), respectively. Relative bioavailability of the test formulation was calculated as 94% (ISDN) and 96% (IS-5-MN). Maximum plasma concentrations of ISDN (IS-5-MN) were determined for the test preparation as 14.3 +/- 3.1 ng/ml (265 +/- 45 45 ng/ml) and as 22.8 +/- 12.6 ng/ml (287 +/- 59 ng/ml) for the reference product. HVD-values were for the test preparation 4.5 +/- 1.3 h (ISDN) and 8.5 +/- 1.3 h (IS-5-MN) and for the reference formulation 3.1 +/- 1.2 h (ISDN) and 8.1 +/- 1.4 (IS-5-MN).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Performance tests and quality control of cathode ray tube displays.

Spatial resolution, noise, characteristic curve, and absolute luminance are the essential parameters that describe physical image quality of a display. This paper presents simple procedures for assessing the performance of a cathode ray tube (CRT) in terms of these parameters as well as easy set up techniques. The procedures can be used in the environment where the CRT is used. The procedures are based on a digital representation of the Society of Motion Pictures and Television Engineers pattern plus a few simple other digital patterns. Additionally, measurement techniques are discussed for estimating brightness uniformity, veiling glare, and distortion. Apart from the absolute luminance, all performance features can be assessed with an uncalibrated photodetector and the eyes of a human observer. The measurement techniques especially enable the user to perform comparisons of different display systems.

Data Display↗
PubMed1989

Gas-liquid chromatography-mass spectroscopy determination of clopamide in plasma.

A gas-liquid chromatography-mass spectroscopy (GLC-MS) method for the determination of clopamide (1) in human plasma was developed to evaluate the pharmacokinetics and bioavailability of 1 in humans. The method is specific, sensitive, and rapid and allows routine analysis as required for extensive pharmacokinetic studies. The assay procedure involves addition of furosemide (2) as an internal standard to plasma, separation on Sep Pack-C18 cartridges, elution by ether: methanol (1:1), evaporation, and subsequent derivatization with trimethylanilinium hydroxide in methanol (Methelute). Then, 5 microL of the reaction mixture is injected into a GLC-MS system which consists of a 1% SE-30 on Gas Chrom Q (100-120 mesh) glass column. The MS information was obtained under the following conditions: ionization beam energy 70 eV, ion source 200 degrees; and m/e 372 for single ion monitoring. The retention times for 1 and 2 were 0.6 and 1.0 min, respectively. The limit of detection is 10 ng/mL of 1 in plasma and the calibration curve was shown to be linear between 10 and 500 ng/mL of 1. After repeated analysis of spiked plasma samples, the coefficient of variation ranged from 5.1 to 8.3%. The recovery from the extraction procedure was 92 +/- 2.2%. Spiked samples frozen at -20 degrees C were stable for at least 8 weeks. The method has been successfully used in a pharmacokinetic study with po dosing of 5 mg of 1 to eight healthy volunteers. Peak plasma concentrations of 197 +/- 56 ng/mL were observed after 1.1 +/- 0.34 h. No measurable concentration of 1 beyond 12 h after dosing was observed.

Adult↗
PubMed1989

Clinical chronopharmacology of oral nitrates.

The clinical-chronopharmacological investigations with oral nitrates (ISDN, IS-5-MN) demonstrate that the drugs' pharmacokinetics and/or hemodynamic effects are circadian phase-dependent. For both an immediate-release and a sustained-release preparation of IS-5-MN peak drug concentrations coincided with peak drug effects after morning but not after evening drug application. Results indicate a circadian phase-dependency in the dose-response relationship of oral nitrates.

Administration, Oral↗
PubMed1989

Bioequivalence studies: single vs multiple dose.

Bioequivalence of different preparations of the same drug substance has gained considerable importance over the last few years due to increasing generic substitution. The procedure that the manufacturer of the generic test preparation has to show bioequivalence with an appropriate reference preparation is scientifically accepted and laid down in international regulations. However, the necessity of single- vs multiple-dose bioequivalence studies has not been discussed in detail with the exception of the Dutch and US guidelines on sustained-release theophylline formulations, where multiple-dose studies are specifically required. This paper compares the conclusions drawn from single- and multiple-dose studies in the same subjects and recommends appropriate pharmacokinetic characteristics.

Adult↗
PubMed1987

Determination of chlormezanone in human plasma after administration of chlormezanone formulations.

In the course of a bioavailability study some 800 plasma samples were analysed by means of HPLC after administration of 5 different chlormezanone formulations to 10 healthy male volunteers. A metabolic product of chlormezanone (I) could not be detected in any of the samples. The results were further verified through mass spectrometric measurements of chlormezanone, extracted from the plasma sample and separated through HPLC, in off-line mode. Chlormezanone is found as an intact molecule in human plasma samples.

Adult↗