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Biomedical subjects

H U Schulz

Publications and source records attributed to H U Schulz.

At least 19 recordsLinked to original sources
PubMed1992

Determination of apovincaminic acid in serum by means of high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of low concentrations in serum of apovincaminic acid, the main metabolite of vinpocetine, is reported. The assay includes a two-step ion-pair extraction with tetrabutylammonium as counter ion. Recovery is ca. 40%. Separation is performed on a narrow-range 5 microns particle size octadecylsilane modified silica packing. Heptanesulphonic acid is the pairing ion in the eluent, and the ultraviolet detection wavelength is 224 nm. Yohimbine serves as the internal standard. The assay is fast, accurate and sensitive quantifying at least 5 ng/ml apovincaminic acid in serum. The method was applied to the analysis of serum samples from aged subjects, treated with a 20-mg dose of vinpocetine.

Chromatography, High Pressure Liquid↗
PubMed1992

Investigation of the bioequivalence of two carbamazepine sustained-release formulations in healthy subjects.

A bioavailability study of two commercial carbamazepine sustained-release formulations was carried out in 14 healthy male subjects in order to compare plasma concentration/time profiles and to determine the relative bioavailability of carbamazepine (CBZ). This randomized study had a single-dose, crossover design and consisted of two trial periods separated by a three-week wash-out period. A sensitive, validated HPLC method was used to analyze plasma carbamazepine levels. Bioequivalence was only accepted for the test (Timonil 600 retard from Desitin Arzneimittel GmbH) and reference preparations (T and R) if the 90% confidence interval (parametric or non-parametric) for the ratios of the median values of the target variables was completely within the bioequivalence range. The following values were found for relative bioavailability: T/R: AUC = 109.6 (101.5-116.5)%, MRT = 96.4 (92.0-100.4)%, HVD = 92.4 (85.0-97.8)%. Applied to these pharmacokinetic data, the requirements for bioequivalence are met when the inclusion rule is used.

Adult↗
PubMed1992

Presentation of results from bioequivalence studies.

Based on general guidelines and requirements for the design and analysis of bioequivalence studies, specific recommendations are made for the presentation of results, both in tabular and graphical form. This is done by means of two examples, one of a single-dose study and one of a multiple-dose study. The recommendations in this paper are twofold. Firstly, a complete and rather detailed presentation of results is given, which practically corresponds to the standard of research reports. Secondly, a subset of this is suggested for publication. It gives the essential results for bioequivalence assessment in a standardized form. From an editorial point of view, it would be highly appreciated if the papers submitted for publication were always accompanied by a complete presentation including the individual concentration/time data and the various steps of calculation. This would speed up peer review and ultimately improve and harmonize the standard of bioequivalence publications.

Adult↗
PubMed1992

Investigations into the relative bioavailability of carbamazepine after single oral administration of three test batches of a carbamazepine-containing sustained release formulation in healthy subjects.

A bioavailability study with three test batches of a sustained release formulation of carbamazepine, which differed only in their in vitro dissolution profiles, was performed in 18 healthy subjects to compare the respective plasma concentration profiles and to determine the relative bioavailability of carbamazepine (CBZ). This investigation was designed to examine the extent to which these differences in dissolution properties can be determined from the results of in vivo tests. The randomized, single-dose, crossover study comprised three experimental periods, separated by washout intervals of three weeks' duration. A sensitive, validated HPLC method was used for the analysis of serum carbamazepine concentrations. Bioequivalence was only accepted if the 90% confidence interval (parametric or nonparametric) for the quotients of the mean values of the variables for each test and reference preparation was completely within the bioequivalence range. For this calculation, all three test preparations were compared with one another. The following relative bioavailability values were obtained: A/B: AUC = 87% (83%, 92%), MRT = 106% (103%, 109%), HVD = 109% (105%, 113%). C/B: AUC = 106% (101%, 110%), MRT = 98% (96%, 99%), HVD = 87% (82%, 91%). C/A: AUC = 124% (117%, 130%), MRT = 92% (89%, 94%), HVD = 79% (74%, 84%). There was a positive correlation between the in vitro dissolution rates of the different test batches and the respective degree of carbamazepine absorption as determined in vivo, while an inverse correlation existed between the in vitro dissolution rates on one side and the mean residence time (MRT) as well as the half value duration (HVD) on the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Pharmaceutical and biopharmaceutical quality of a sustained release carbamazepine preparation: a contribution to quality assurance.

Side effects observed during treatment with non-sustained release carbamazepine preparations are often due to the steep rise in plasma carbamazepine concentrations. To maintain plasma levels with only minor fluctuations between narrow limits, sustained release formulations have been developed which release the active constituent at a constant rate which is not too high. Bioavailability tests (single dosage, crossover design) and several investigations into the dissolution profile were carried out on three test batches of a sustained release carbamazepine preparation (Timonil 300 retard). The aim was a release model which, in the context of quality assurance, would not only facilitate reliable statements with regard to batch conformity, but would also be validated in respect of pharmacokinetic parameters such as rate of absorption and bioavailability. Correlations between mean dissolution times (MDT) and mean absorption times (MAT) at level B were found [Skelly et al. 1990]. A dissolution test differing from the pharmacopoeial tests was selected, which permitted the assessment of both batch conformity and biopharmaceutical batch quality.

Absorption↗
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↗
PubMed1992

Presentation of results from bioequivalence studies.

Based on general guidelines and requirements for the design and analysis of bioequivalence studies, specific recommendations are made for the presentation of results, both in tabular and graphical form. This is done by means of two examples, one of a single-dose study and one of a multiple-dose study. The recommendations in this paper are twofold. Firstly, a complete and rather detailed presentation of results is given, which practically corresponds to the standard of research reports. Secondly, a subset of this is suggested for publication. It gives the essential results for bioequivalence assessment in a standardized form. From an editorial point of view, it would be highly appreciated if the papers submitted for publication were always accompanied by a complete presentation including the individual concentration/time data and the various steps of calculation. This would speed up peer review and ultimately improve and harmonize the standard of bioequivalence publications.

Delayed-Action Preparations↗
PubMed1991

Lack of influence of pantoprazole on the disposition kinetics of theophylline in man.

The potential influence of pantoprazole (BY1023/SK&F96022), a newly developed selective inhibitor of the gastric H+,K(+)-ATPase, on therapeutic serum theophylline concentrations was investigated in a crossover study in 8 healthy male volunteers (age 25-30 [median 27] years, body weight 63-80 [median 68] kg). Steady-state serum theophylline concentrations were obtained by a two-step intravenous infusion scheme of approximately 350 mg theophylline each over 0.5 h and subsequently over approximately 10 h, respectively. In the test period, 30 mg pantoprazole were injected over 2 min on 5 consecutive days and theophylline was infused on day 4. In the reference period, placebo was administered i.v. on 2 consecutive days and theophylline on day 1. Serum pantoprazole concentrations were measured up to 12 h, serum theophylline concentrations up to 36 h. Pantoprazole was well tolerated with and without theophylline. There were no clinically relevant changes in blood pressure, heart rate, ECG and routine clinical laboratory parameters. Primary characteristic for confirmative assessment of no interaction was the area under the concentration/time curve (AUC). Lack of interaction in the sense of equivalence was concluded both for theophylline (with and without pantoprazole) and pantoprazole (with and without theophylline), as the 90%-confidence intervals of the AUC-ratio test/reference were within the equivalence range of 0.8 to 1.25. Further explorative analysis of theophylline disposition kinetics revealed this inclusion also for clearance and volume of distribution, but not for the half-life. In the case of pantoprazole, the corresponding 90%-confidence intervals for any of the secondary characteristics clearance, volume of distribution and half-life were within the above mentioned range.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1991

A study relating to bioavailability and renal elimination of bismuth after oral administration of basic bismuth nitrate.

The extent to which bismuth is absorbed following single and multiple oral administration of basic bismuth nitrate was investigated in healthy male subjects. The blood concentration of bismuth and the amounts excreted in urine and feces were determined. The results show that only a small fraction of the administered bismuth dose given in this form is absorbed. Existing differences in the absorption kinetics between this relatively insoluble bismuth salt and colloidal bismuth citrate are discussed.

Administration, Oral↗
PubMed1990

Decreased survival rate of pancreatic acinar cells isolated from rats with acute pancreatitis.

Viable acinar cells were isolated from normal rat pancreas as well as from pancreata pretreated in situ by a short-term ischemia without and with reperfusion, induction of a pancreatic juice edema, and acute pancreatitis (AP), respectively. The isolated cells were incubated at 37 degrees C in an oxygenated Krebs-Henseleit bicarbonate buffer lacking any nutrient. As an analog to in vivo acinar cell necrosis, the decline of the isolated cells was followed up in vitro. During the first 5-6 h of incubation, the percentage of damaged cells increased only slightly. A second phase of about 30 min followed, during which nearly all residual cells died. The mean half-life (t50) of the cells in all experimental groups ran to about 330 min, with the exception of the AP group (t50 = 132 min). The importance of an intact energy metabolism to prevent premature cell killing was underlined indirectly by the diminished t50 (about 120 min in all groups) of the cells exposed to excess 2,4-dinitrophenol, an uncoupler of oxidative phosphorylation. The results suggest that experimental AP induced by a combination of biliary-pancreatic duct obstruction, stimulation of pancreatic secretion, and short-term pancreatic ischemia with subsequent reperfusion finds a reflection within the acinar cells themselves and that these effects are not clouded by the isolation procedure. Thus, the application of acinar cells isolated from pancreatic glands pretreated in situ may offer a new tool for pathophysiological research into AP at the cellular level.

2,4-Dinitrophenol↗
PubMed1989

Glibenclamide steady state plasma levels during concomitant vinpocetine administration in type II diabetic patients.

The influence of vinpocetine on glibenclamide steady state plasma levels was investigated in 18 patients suffering from type II diabetes and symptoms of dementia. During the study patients continued to follow their individual scheme of glibenclamide intake and 10 mg vinpocetine were given t.i.d. from day 2 to 5. Glibenclamid as well as glucose plasma levels were repeatedly determined on the first day of the trial and compared to those on the fifth day where patients had received additional vinpocetine medication for four days. Time point comparisons were employed to exclude clinically relevant changes of glibenclamide bioavailability and kinetics. The data of this trial show that vinpocetine does not interfere with the kinetics of glibenclamide. Thus, it can be concluded that the comedication with vinpocetine does not represent a potential risk for a possible drug interaction in case of antidiabetics treatment with glibenclamide.

Blood Glucose↗
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↗
PubMed1988

Effects of pancreatic acinar cell surface antibodies and complement on isolated rat acinar cells in vitro.

Surface directed pancreatic acinar cell antibodies raised by immunization of rabbits with suspensions of viable isolated rat acinar cells were utilized to study immune cytolytic processes as a model of in vitro pancreatic injury. The antibodies produced were bound to rat pancreatic acinar cell surface determinants and significantly damaged freshly separated acinar cells by immune cytolytic mechanisms. Addition of complement accelerated the cytolytic effects on the target cells in a dose-dependent manner. The decline of acinar cells was dependent only on the presence of the immune cytolytic potential and not on the number of already damaged cells. Morphologic changes in the cells induced by the agents applied were revealed by both transmission and scanning electron microscopy. The presented experimental model seems a valuable tool for further investigations at the cellular level into the contribution of primarily occurring acinar cell injury in triggering the subsequent pathophysiological mechanisms initiating autodigestion of the pancreatic gland in the pathogenesis of acute pancreatitis.

Animals↗
PubMed1988

An optimized procedure for isolation of rat pancreatic acinar cells.

A simple and inexpensive procedure is described which allows reproducibly the isolation of rat pancreatic acinar cells. Using only small quantities of commercially available collagenase without addition of any further protease, a cell population consisting of about 95% of acinar cells can be obtained within about 95 min. Cell yield is 40% as calculated on a dry weight basis. Enzyme activities measured within final suspensions of isolated cells are: amylase, 1.17 +/- 0.27 amylase units.(mg d.w.)-1; lipase, 23.78 +/- 6.02 nkat.(mg d.w.)-1 and alanine aminotransferase, 0.895 +/- 0.236 nkat.(mg d.w.)-1. Isolated cells are morphologically intact as seen by electron microscopy and retain their viability for more than 3 h, even when incubated at 37 degrees C without any substrate and protease inhibitor, as revealed by their ability to exclude trypen blue. Therefore, acinar cells isolated in this manner may prove useful for investigations at cellular level into pathogenetic mechanisms underlying pancreatic diseases.

Alanine Transaminase↗