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D Hauschke

Publications and source records attributed to D Hauschke.

35 records · Page 2Linked to original sources
PubMed1994

Effects of lung surfactant factor (LSF) treatment on gas exchange and histopathological changes in an animal model of adult respiratory distress syndrome (ARDS): comparison of recombinant LSF with bovine LSF.

Repetitive lung lavage of adult rats leads to lung injury similar to ARDS resulting in poor gas exchange, protein leakage and infiltration of polymorphonuclear neutrophils (PMN) into the alveolar spaces (J Appl Physiol 1983; 55: 131-138). In a previous dose response comparison we have demonstrated that poor gas exchange could be improved by lung surfactant factor (LSF) instillation soon after lavage. Since Surfacten (Tokyo Tanabe Co. Ltd., Tokyo, Japan) was described in vitro to inhibit PMN activity, we compared this preparation with a Recombinant LSF preparation (Byk Gulden, Konstanz, Germany; phospholipids plus human identical surfactant protein C) at doses of 25, 50 and 100 mg/kg body weight. Their efficacy was compared with an untreated control group with respect to improving gas exchange, inhibition of hyaline membrane formation and inhibition of the inflammatory response after multiple lavage. Tracheotomized rats were pressure-controlled ventilated (Siemens Servo Ventilator 900C, Sweden) with 100% oxygen at a respiratory rate of 30 breaths/min, inspiration:expiration ratio of 1:2, peak inspiratory pressure (PIP) of 28 cmH2O at positive end-expiratory pressure (PEEP) of 8 cmH2O. Two hours after LSF administration PEEP was reduced from 8 to 6 cmH2O (first PEEP-reduction), from 6 to 3 (second reduction) and from 3 to 0 cmH2O (third reduction) and finally raised to 8 cmH2O. Results for the averaged partial arterial oxygen pressure [PaO2 (mmHg)] of the 2 h period [PaO2(5'-120')] and for the PaO2 during the second PEEP reduction [PaO2(PEEP23/3] were calculated. Both LSF preparations caused a dose-dependent increase of the PaO2 (5'-120') and the PaO2(PEEP23/3). Similarly, the formation of hyaline membranes was inhibited by both LSF preparations in a dose-dependent manner. Inhibition of the inflammatory response (infiltration of PMN) was not effected by either of the LSF preparations at any dose level. The described variations in ventilator settings are useful to evaluate the deflation stability and re-expansion potential of different LSF preparations. The reported results give evidence that prevention of atelectasis by LSF treatment improves gas exchange and inhibits formation of hyaline membranes, leading to the conclusion that LSF treatment may be a promising therapy in ARDS patients.

Animals↗
PubMed1994

Choice of characteristics and their bioequivalence ranges for the comparison of absorption rates of immediate-release drug formulations.

For immediate release drug formulations the maximum concentration (Cmax), the time to the maximum concentration (tmax), and the ratio Cmax/AUC have been suggested as absorption rate characteristics. Although tmax is easier to interpret as absorption rate characteristic than Cmax and Cmax/AUC, the latter are generally preferred in practice because these characteristics can be observed with higher precision, and are easier to handle statistically than tmax. In this paper we propose a strategy for setting appropriate bioequivalence ranges for tmax and Cmax/AUC, and for choosing the best characteristic for the comparison of absorption rates when planning a bioequivalence study. This involves motivating the bioequivalence range on that scale which is most convenient for that purpose, namely in terms of differences in tmax. Exploiting the pharmacokinetic relationship between tmax and Cmax/AUC this bioequivalence range is then translated into the corresponding bioequivalence range for Cmax/AUC. The characteristic that gives the greatest power to show bioequivalence can then be specified as the primary absorption rate characteristic. For drugs with short elimination half-lives, or short fastest disposition half-lives if the drug concentrations follow a higher compartmental model, Cmax/AUC is the best characteristic, but for drugs with long elimination or fastest disposition half-lives tmax can be superior to Cmax/AUC.

Absorption↗
PubMed1994

Presentation of the intrasubject coefficient of variation for sample size planning in bioequivalence studies.

Bioequivalence studies are generally performed as crossover studies and, therefore, information on the intrasubject coefficient of variation is needed for sample size planning. Unfortunately, this information is usually not presented in publications on bioequivalence studies, and only the pooled inter- and intrasubject coefficient of variation for either test or reference formulation is reported. Thus, the essential information for sample size planning of future studies is not made available to other researchers. In order to overcome such shortcomings, the presentation of results from bioequivalence studies should routinely include the intrasubject coefficient of variation. For the relevant coefficients of variation, theoretical background together with modes of calculation and presentation are given in this communication with particular emphasis on the multiplicative model.

Humans↗
PubMed1992

Sample size determination for bioequivalence assessment using a multiplicative model.

In bioequivalence studies Cmax and AUC serve as the primary pharmacokinetic characteristics of rate and extent of absorption. Based on pharmacokinetic relationships and on empirical evidence, the distribution of these characteristics corresponds to a multiplicative model, which implies a logarithmic normal distribution in the case of a parametric analysis. Hence, consideration is given to exact and approximate formulas of sample sizes in the case of a multiplicative model.

Methods↗
PubMed1992

Comparison of the ECL-cell frequency in the stomachs of 3 different rat strains.

Three different rat strains, Sprague-Dawley, Wistar and Fischer 344, were treated for 3 months with 2 doses (0.8; 4 mg/kg) of the gastric acid suppressing ATPase inhibitor pantoprazole. The gastrin levels were determined, the height of the mucosa measured and the number of enterochromaffin-like (ECL) cells counted. Because these cells were stained according to the method of Grimelius they were designated as GPC (Grimelius positive cells). Under 4 mg/kg, the gastrin levels were increased 8 hours after administration, but fell again after 24 h. The Fischer rats showed the highest value. Also the height of the mucosa was increased under 4 mg/kg. A trend towards an increased mucosal height was noticeable even at 0.8 mg/kg. The number of GPC was determined in 2 ways: 1) without taking the mucosal height into account, 2) taking the height into account. An increase in GPC was observed at 4 mg/kg with both methods.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

Effect of changing the bioequivalence range from (0.80, 1.20) to (0.80, 1.25) on the power and sample size.

International harmonization of guidelines for bioequivalence assessment has led to a wide acceptance of the multiplicative model for the extent and rate characteristics AUC and Cmax and--in consistency with this--of the bioequivalence range (0.80, 1.25). The effect of this change from (0.80, 1.20) on the power of the two one-sided test procedure and the sample sizes based thereon is investigated as a function of the within-subject coefficient of variation (CV) and the ratio mu T/mu R of expected medians for test and reference. The relative reduction in sample size is practically zero for mu T/mu R < or = 0.9 and then gradually increases as mu T/mu R approaches 1.2. At mu T/mu R = 1, the reduction is up to 20%. For a fixed ratio mu T/mu R this reduction increases with the coefficient of variation, reaching a plateau at a CV of about 25%.

Models, Statistical↗
PubMed1992

Sample size determination: extended tables for the multiplicative model and bioequivalence ranges of 0.9 to 1.11 and 0.7 to 1.43.

For the two-period crossover design and a multiplicative model (logarithmic normal distribution) the decision procedure of choice is based on the inclusion of the shortest 90%-confidence interval for the ratio of expected medians for test and reference in the equivalence range. This inclusion rule is equivalent to the two one-sided tests procedure. Sample sizes based on the power of the latter have been given by Diletti et al. [1991] for an equivalence range of 0.8 to 1.25. Corresponding tables for the tighter equivalence range of 0.9 to 1.11 as well as for the wider range of 0.7 to 1.43 are given in this amendment.

Confidence Intervals↗
PubMed1992

A distribution-free procedure for the statistical analysis of bioequivalence studies.

In bioequivalence assessment, the consumer risk of erroneously accepting bioequivalence is of primary concern. In order to control the consumer risk, the decision problem is formulated with bioinequivalence as hypothesis and bioequivalence as alternative. In the parametric approach, a split into two one-sided test problems and application of two-sample t-tests have been suggested. Rejection of both hypotheses at nominal alpha-level is equivalent to the inclusion of the classical (shortest) (1-2 alpha) 100%-confidence interval in the bioequivalence range. This paper demonstrates that the rejection of the two one-sided hypotheses at nominal alpha-level by means of nonparametric Mann-Whitney-Wilcoxon tests is equivalent to the inclusion of the corresponding distribution-free (1-2 alpha) 100%-confidence interval in the bioequivalence range. This distribution-free (nonparametric) approach needs weaker model assumptions and hence presents an alternative to the parametric approach.

Adult↗
PubMed1992

Update on the statistical analysis of bioequivalence studies.

Statistical methods to assess bioequivalence of a test and a reference formulation are reviewed with emphasis on the distribution of bioequivalence characteristics and the consumer risk of erroneously accepting bioequivalence. Among the procedures not exceeding a nominal consumer risk of 5%, the one with an acceptably small producer risk of erroneously rejecting bioequivalence is selected. With the exception of tmax, the following strategy is recommended: a decision in favour of bioequivalence is made if the shortest 90%-confidence interval for the ratio of the expected medians is in the bioequivalence range for the chosen characteristics of rate and extent of absorption. If the assumption of a logarithmic normal distribution is not valid, the analogous nonparametric (distribution-free) 90%-confidence interval, which is also based on the two-sample approach for the sequences reference/test and test/reference, is the procedure of choice. The issue of a modification of the bioequivalence range of 80-120% to other values for bioequivalence characteristics other than AUC (e.g. Cmax) is also addressed. Finally, a decision rule for tmax is presented.

Chemistry, Pharmaceutical↗
PubMed1992

Sample size determination for bioequivalence assessment by means of confidence intervals.

The statistical analysis of bioequivalence assessment has been consolidated in recent years through the work of Schuirmann [1987], Westlake [1988] and Hauschke et al. [1990], and this has been reflected in the CPMP Note for Guidance on Bioavailability and Bioequivalence and in the joint recommendations of the APV (International Association for Pharmaceutical Technology) and ZL (Central Laboratories of German Pharmacists) during a recent workshop in support of EC-Guidelines [Blume et al. 1990]. Since the decision procedure based on the inclusion of the shortest 90%-confidence interval in the bioequivalence range is the procedure of choice, and as this is equivalent to the two one-sided tests procedure, the sample size determination is based on the power of the latter. Following the approach of Phillips [1990] for the additive model, corresponding nomograms for the more relevant multiplicative model are given in this paper for various ratios of the expected means for test and reference and various coefficients of variation.

Confidence Intervals↗
PubMed1992

Sample size determination: extended tables for the multiplicative model and bioequivalence ranges of 0.9 to 1.11 and 0.7 to 1.43.

For the two-period crossover design and a multiplicative model (logarithmic normal distribution) the decision procedure of choice is based on the inclusion of the shortest 90%-confidence interval for the ratio of expected medians for test and reference in the equivalence range. This inclusion rule is equivalent to the two one-sided tests procedure. Sample sizes based on the power of the latter have been given by Diletti et al. [1991] for an equivalence range of 0.8 to 1.25. Corresponding tables for the tighter equivalence range of 0.9 to 1.11 as well as for the wider range of 0.7 to 1.43 are given in this amendment.

Humans↗
PubMed1991

Sample size determination for bioequivalence assessment by means of confidence intervals.

The statistical analysis of bioequivalence assessment has been consolidated in recent years through the work of Schuirmann [1987], Westlake [1988] and Hauschke et al. [1990], and this has been reflected in the CPMP Note for Guidance on Bioavailability and Bioequivalence and in the joint recommendations of the APV (International Association for Pharmaceutical Technology) and ZL (Central Laboratories of German Pharmacists) during a recent workshop in support of EC-Guidelines [Blume et al. 1990]. Since the decision procedure based on the inclusion of the shortest 90%-confidence interval in the bioequivalence range is the procedure of choice, and as this is equivalent to the two one-sided tests procedure, the sample size determination is based on the power of the latter. Following the approach of Phillips [1990] for the additive model, corresponding nomograms for the more relevant multiplicative model are given in this paper for various ratios of the expected means for test and reference and various coefficients of variation.

Humans↗
PubMed1990

A distribution-free procedure for the statistical analysis of bioequivalence studies.

In bioequivalence assessment, the consumer risk of erroneously accepting bioequivalence is of primary concern. In order to control the consumer risk, the decision problem is formulated with bioinequivalence as hypothesis and bioequivalence as alternative. In the parametric approach, a split into two one-sided test problems and application of two-sample t-tests have been suggested. Rejection of both hypotheses at nominal alpha-level is equivalent to the inclusion of the classical (shortest) (1-2 alpha) 100%-confidence interval in the bioequivalence range. This paper demonstrates that the rejection of the two one-sided hypotheses at nominal alpha-level by means of nonparametric Mann-Whitney-Wilcoxon tests is equivalent to the inclusion of the corresponding distribution-free (1-2 alpha) 100%-confidence interval in the bioequivalence range. This distribution-free (nonparametric) approach needs weaker model assumptions and hence presents an alternative to the parametric approach.

Adult↗
PubMed1990

Update on the statistical analysis of bioequivalence studies.

Statistical methods to assess bioequivalence of a test and a reference formulation are reviewed with emphasis on the distribution of bioequivalence characteristics and the consumer risk of erroneously accepting bioequivalence. Among the procedures not exceeding a nominal consumer risk of 5%, the one with an acceptably small producer risk of erroneously rejecting bioequivalence is selected. With the exception of tmax, the following strategy is recommended: a decision in favour of bioequivalence is made if the shortest 90%-confidence interval for the ratio of the expected medians is in the bioequivalence range for the chosen characteristics of rate and extent of absorption. If the assumption of a logarithmic normal distribution is not valid, the analogous nonparametric (distribution-free) 90%-confidence interval, which is also based on the two-sample approach for the sequences reference/test and test/reference, is the procedure of choice. The issue of a modification of the bioequivalence range of 80-120% to other values for bioequivalence characteristics other than AUC (e.g. Cmax) is also addressed. Finally, a decision rule for tmax is presented.

Biometry↗
PubMed1985

[Accuracy of halothane vaporizers with respect to temperature, carrier gas composition and gas flow rate].

Since the precise measurement of halothane-concentration in the patients gas support during routine anesthesia still requires much effort, the accuracy of the vaporizers halothane output remains important for the safety of anesthesia and the education of younger anesthesiologists. In the present study 30 halothane vaporizers (14 Fluotec Mark 3/Cyprane Ltd., 12 Vapor 19/Dräger, 4 Abingdon/Penlon) were removed from the operating rooms in the University Hospital Göttingen to test their accuracy. The measurements were performed with a masspectrometer under standardized laboratory conditions with varied temperatures (10 degrees, 21 degrees, 35 degrees C), gasflows (3, 5, 8 l/min) and compositions of carrier gas (100% O2, N2O/O2 = 2/1). All vaporizers in this study showed a light tendency to higher halothane outputs for low concentration adjustments and to distinct lower outputs for higher concentration adjustments. The Vapor 19 vaporizers compensated well with changes of temperatures and gasflows but had a distinct dependency on carriers gas compositions. The Fluotec Mark 3 vaporizers output depended on the temperature and gasflow but was almost unaffected by the carrier gas composition. Tremendous deviations appeared with the Abingdon vaporizers, which seamed to be without any temperature compensation and which were highly gas flow dependent. It can be concluded from our results that vaporizers according to their construction tend to be imprecise.

Anesthesia↗