Biomedical subjects

G Pabst

Publications and source records attributed to G Pabst.

51 records · Page 3Linked to original sources

PubMed1991

[Plasma and urine kinetics of amitriptyline oxide and its metabolites. Comparison of intravenous infusion and oral administration in volunteers].

The study objective was to obtain detailed information on the plasma and urine kinetics of amitriptylinoxide (CAS 4317-14-0) and its metabolites. For this reason, 60 mg of amitriptylinoxide was administered to 12 subjects, both by intravenous infusion and by oral dosage, in a study performed according to a randomized two-way cross-over design. In plasma, we succeeded in analyzing the metabolites amitriptyline and nortriptyline in addition to the parent substance amitriptyloxide. The tests for the parent substance amitriptylinoxide revealed maximum plasma levels of 721 and 686 ng/ml at 1.96 h (i.v. infusion) and 0.82 h (oral formulation), respectively. Mean values of 2331 (infusion) and 1714 h.ng/ml (oral formulation) were determined for the area under the curve from time 0 to infinity AUC (0-infinity). We also produced a comprehensive evaluation of amitriptyline, however, this was not possible for the metabolite nortriptyline. In urine, we succeeded in a reliable quantification of 4 metabolites, namely cis-OH-amitriptylinoxide, trans-OH-amitriptylinoxide, amitriptyline and OH-nortriptyline, in addition to the parent substance amitriptylinoxide. In individual samples, nortriptyline, cis-OH-amitriptyline and trans-OH-amitriptyline were additionally identified. In the course of the study, there were no reports or observations of any adverse reactions in addition to the side effects known for amitriptylinoxide from literature. There were no clinically relevant differences in tolerability observed between these two preparations.

Administration, Oral↗

PubMed1990

Review of methods and criteria for the evaluation of bioequivalence studies.

Guidelines for the performance and analysis of bioequivalence studies are not very specific. The advantages and disadvantages of the following methods and tests are discussed: analysis of variance by summation or by use of general linear models, nonparametric procedures, aposteriori probabilities and tests on the normality of residuals and on the variability of the results. Arguments for or against an analysis of data after logarithmic transformation versus analysis of untransformed data are presented. If the confidence intervals lie within certain limits, preparations may be considered equivalent. The criteria leading to those limits are discussed. It is recommended that concentration-dependent data of bioequivalence studies be evaluated by analysis of variance after logarithmic transformation, applying general linear models. Data that by theoretical reasons cannot be normally or log-normally distributed should be analysed by nonparametric methods. Otherwise these methods can only be recommended if a significant deviation from normality has been noted and only for two-way cross-over designs. For a geometric evaluation (after logarithmic transformation) the regions of acceptance should be symmetrical in the logarithm, e.g. (80%, 125%).

Analysis of Variance↗

PubMed1990

[Absorption profile and absolute bioavailability of a theophylline--retard preparation].

Absorption Profile and Absolute Bioavailability of a Theophylline Retard Preparation. In a single-dose cross-over study with 16 healthy male nonsmoking volunteers the absorption profile and absolute bioavailability of the retard pellets contained in all dosage strengths of Bronchoretard (100, 200, 350, 500 mg anhydrous theophylline) were investigated. One capsule (500 mg theophylline) was given after an evening meal. The reference treatment consisted of an i.v. infusion over 8 h in a total dosage of 350 mg theophylline. Plasma concentration-time profiles were evaluated for 72 h after dosing, respectively start of infusion. Theophylline was measured by high-performance liquid chromatography (HPLC). Absorption profiles (Wagner-Nelson) were derived and the absolute bioavailability was calculated. For the retard pellets a liberation/absorption of zero order for 12 h could be noted; the dose-corrected mean absolute bioavailability was 88%. The assumptions of an investigation on absolute bioavailability are discussed and the limitations on generalizability resulting therefrom.

Absorption↗

PubMed1990

[Early evening administration of ranitidine in therapy of duodenal ulcer].

In this randomized clinical study the effect of 300 mg ranitidine given either after an early evening meal (abt. 6 p.m.) (n = 136) or at bedtime (abt. 10 p.m.) (n = 145) was investigated in 279 patients with an acute duodenal ulcer (79 women, 200 men, age median 40 years). To provide a double blind design, patients of each therapy group were given a placebo tablet either at 10 p.m. or at 6 p.m. (double dummy technique). After 2 and 4 weeks of therapy, the healing rates for the early resp. late evening doses were 75.6% and 65.9% (p = 0.054) and 95.5% and 94.2%, respectively. The healing rates for patients with an ulcer diameter between 5 mm and 9.5 mm and with a case history of duodenal ulcer, however, were significantly higher for the early evening doses of 300 mg ranitidine (85 vs. 65%, p less than 0.01, and 75 vs. 60%, p less than 0.05). The study results indicate that an early (abt. 6 p.m.) as well as a late (abt. 10 p.m.) evening doses of 300 mg ranitidine have a comparable positive effect on the healing of an acute duodenal ulcer, with the early evening doses having advantages in special patient groups.

Adolescent↗

PubMed1990

[Comparison of the effect and tolerability of two glibenclamide preparations with different release rates].

In a double-blind, randomized, multicenter, two-way crossover study, efficacy and tolerability of two glibenclamide (CAS 1028-21-8) preparations with different rates of release were compared during a 28 day long-term treatment period for each preparation. It involved 80 patients with diabetes mellitus type II difficult to stabilize orally, who had received preliminary glibenclamide treatment. The switching from one treatment to the other in particular was strictly controlled: day profiles on glucose and insulin were prepared on the last day of the long-term therapy period and again on the first two days of the next long-term therapy period. Halfway through each treatment period and on the last day of each therapy period, the glucose content of the 24 h urine was determined in order to assess diabetes stabilization. The quality of diabetes stabilization and tolerability being comparable for both treatments, there were no statistically significant differences determined for AUC, Cmin, Cmax, tmin and tmax in the insulin day profile and glucose day profile on switching from treatment A (Glibenclamid-ratiopharm) to B (reference preparation) nor from B to A. The tolerability of both preparations was very good.

Aged↗

PubMed1989

Bioequivalence and pharmacodynamics of a modified glibenclamide formulation in healthy volunteers.

A glibenclamide preparation (Glycolande N) with a modified galenic formulation was compared with a marketed standard preparation for bioequivalence and hypoglycaemic action after single oral administration of 3.5 mg. Twelve healthy male volunteers participated in this open two-way cross-over study. The confidence intervals around the mean values of the standard preparation were all in the range of +/- 20%. No significant differences were found between both formulations for Cmax, Tmax, AUC1 and AUC3. The glucose profiles were virtually equal. Both preparations are regarded as bioequivalent and therapeutically equivalent.

Adult↗

PubMed1989

[Bioavailability and pharmacokinetics of a new nifedipine preparation in healthy volunteers].

In the course of this trial the bioavailability and the essential pharmacokinetic parameters of a newly developed 10 mg nifedipine preparation were to be determined in comparison to a marketed reference preparation after single oral administration. For this purpose, the test and the reference preparation were examined in 16 healthy volunteers according to a randomized 2-way cross-over design (latin square), blood samples were withdrawn up to 16 h p.a. and plasma concentrations of nifedipine and NPO (primary metabolite of nifedipine) were quantified by a HPLC method. Both preparations led to mean maximum concentrations of nifedipine in plasma of 110 mg/ml about 0.5 h p.a.; the mean termial half-lives were 1.8 h (test preparation) and 1.7 h (reference preparation). The data found for the metabolite NPO largely corresponded to those of the parent substance, thus equal metabolisation and adequate pharmaceutical quality of the two galenics may be presumed. Statistical comparison (ANOVA, Pratt-Wilcoxon test) did not reveal any significant differences between the test and reference preparation and, apart from a minor deviation, confidence intervals according to Westlake were sufficiently small, such that the two formulations may be considered bioequivalent. No differences of clinical relevance were detected between the two preparations in assay. The undesired side effects/concomitant symptoms known after nifedipine administration were observed.

Adult↗

PubMed1986

Hemopoietic reconstitution after bone marrow transplantation.

Forty-one patients underwent bone marrow transplantation (BMT) for treatment of severe aplastic anemia or hematologic malignancies. Hemopoietic reconstitution after BMT was monitored by peripheral blood counts, counts of bone marrow cellularity, and clonal assays for hemopoietic progenitors (CFUc, CFUe, and BFUe), along with bone marrow morphology. The number of transplanted nucleated cells and the number of transplanted progenitors (CFUc, CFUe, and BFUe) correlated significantly with the time of reticulocyte recovery. The number of transplanted CFUc correlated significantly with the time of granulocyte recovery. Platelet recovery occurred late and showed large variations. No correlation between the transplanted cells and the recovery of nucleated cells or hemopoietic progenitors (CFUc, CFUe, and BFUe) in the bone marrow was found. Bone marrow cellularity and hemopoietic progenitors showed a rapid, but incomplete, recovery during the first 56 days after BMT. Hematologic studies on seven long-term survivors with an uncomplicated posttransplantation course revealed subnormal bone marrow cellularity and hemopoietic progenitor incidence up to three years after BMT, despite normal peripheral blood counts. The low progenitor incidence could be explained by a proliferative defect of the stem cells, compensated for by an amplification in the more differentiated compartment of hemopoiesis.

Anemia, Aplastic↗

PubMed1986

[Pharmacokinetics and bioavailability of diphenhydramine in man].

By the presented study the relative bioavailabilities and some important pharmacokinetic parameters should be evaluated after oral application of a single-dose of three different diphenhydramine (DPH, 2-diphenylmethoxy-N,N-dimethylethylamine)preparations in a randomized, cross-over design to 12 healthy volunteers. Additionally, some simple pharmacodynamic measurements of the volunteer's vigilance were performed and the question whether a combination with 8-chlorotheophylline influences the pharmacokinetic and/or pharmacodynamic profile of DPH was investigated. As the test preparations (Benocten as a tablet = A, as a buffered solution = B) contained 50 mg of DPH-HCl, but the reference preparation (= C) only 31 mg of DPH-HCl (+ 23 mg 8-chlorotheophylline), the biometric-statistic calculations had to be done with and without dose correction. Bioequivalence of the preparations could only then be demonstrated when the calculations were done with dose corrections: without these corrections for the reference preparation significantly lower serum levels resulted which hardly can be considered sufficient for exerting a sleep-inducing effect. The addition of 8-chlorotheophylline recommended by some other authors for an enhanced sedative effect could not be substantiated by our results. Peak serum levels of 61 and 53 ng/ml, respectively, for the test preparations and 40 ng/ml for the reference preparation were reached after 2.0 to 2.5 h p.a.; elimination half-lives were between 4 and 6 h. A statistically significant positive correlation could be found for AUC (0-24 h) and the amount excreted in urine in the same period of time, as higher mean serum levels were correlated with higher amounts excreted renally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Pharmacokinetics and bioavailability of three different galenic nifedipine preparations.

In a randomized three-way crossover study with twelve volunteers the bioavailability and main pharmacokinetic parameters of three different galenic formulations of nifedipine (hard gelatine capsule with pellets = preparation A, soft gelatine capsule with liquid nifedipine = preparation B, retard-tablet = preparation C) were determined. Plasma concentrations of nifedipine were measured by capillary gas-liquid chromatography up to 24 h after single dosing as well as up to 48 h after multiple doses of the drugs (steady state). Statistically significant differences between the preparations were found for AUC, Cmax, and Tmax. In all respects preparation A was intermediate to the other preparations. Plasma levels of 40 ng/ml or more were reached for most subjects within the first half hour after application of a single dose of preparation A and under steady state conditions plasma concentrations of 25 ng/ml or more could be upheld with this preparation for a longer time than with the reference retard tablet (preparation C). No accumulation of nifedipine in plasma occurred following multiple dosing.

Adult↗

PubMed1985

[Bioavailability of new nifedipine preparations in man. 1. Pharmacokinetics of nifedipine in the form of sustained-release tablets].

Following a single dose of a 20 mg nifedipine retard-tablet (Pidilat retard or a marketed formulation) to 12 healthy volunteers in a randomized, two-fold cross-over trial the nifedipine plasma levels were quantitatively determined by gas chromatography up to 24 h p.a. The relative bioavailabilities and important pharmacokinetic parameters were calculated and then statistically evaluated for significant differences between the preparations. Approx. 2 h after dosing, peak concentrations of 13 to 74 ng/ml were reached, the minimal therapeutic plasma level of 10-15 ng/ml was - in general - upheld for 10 respectively 8 h. Terminal elimination half-lives were calculated to be 5 and 8 h, respectively. An extrapolation with the obtained data for the expected steady state plasma levels after a twice-a-day dosing showed that the above mentioned therapeutically relevant plasma levels of the unchanged drug are in general achieved for most of the dosage interval. The strong inter- and intraindividual variations of blood levels after nifedipine application, which have already been described by numerous other authors, could also be observed in this study.

Adolescent↗

PubMed1985

[Bioavailability of new nifedipine preparations in man. 2. Bioequivalence of nifedipine in the form of soft gelatin capsules].

In a randomized, two-fold cross-over design 12 healthy volunteers received a normal-release 10 mg nifedipine soft gelatine capsule (Pidilat or a marketed product, respectively). The quantitative determination of the drug in plasma was achieved by gas chromatography up to 24 h p.a. Some important pharmacokinetic parameters and the relative bioavailabilities of the preparations were calculated and subsequently compared statistically: statistically significant differences between the preparations could not be found. Mean peak plasma concentrations of 121.2 +/- 47.3 and 104.5 +/- 32.9 ng/ml were reached approximately 0.5 h p.a. Both plasma level curves were practically identical, with the exception of the obtained absolute peak plasma concentrations. The known strong inter- and intraindividual variations of the plasma levels were found to be less pronounced in this study.

Adolescent↗

PubMed1980

A mathematical model of canine granulocytopoiesis.

The granulocyte cell renewal system of the dog is represented by a mathematical model consisting of the following compartments: The pool of pluripotential stem cells, the committed stem cell pool, divided into a blood and a bone marrow compartment, the proliferation pool, the maturation pool, the reserve pool and the blood pool of functional granulocytes. This chain of compartments is described by a system of non-linear differential equations. Cell losses anyplace in the system provoke increased production in all pools containing cells capable to divide. A reduced number of granulocytes in the blood pool stimulates production of a "granulocyte releasing factor" which mobilizes a rising number of cells to transit from the marrow reserve into the blood pool. The model was simulated on a digital computer. It was found to be capable to reproduce the steady state conditions and it also fits the data of two distinct experimental perturbations of the system both equally well. These perturbations are a loss of proliferating cells as it occurs after the administration of cytostatic drugs and losses of functional cells as they are induced by leukapheresis experiments of differing leukapheresis rates.

Animals↗

PubMedDate not supplied

Bioavailability and pharmacokinetics of a fixed combination of delapril/indapamide following single and multiple dosing in healthy volunteers.

The study objective was to obtain detailed information on the bioavailability and pharmacokinetics of the new fixed combination of delapril and indapamide following single and multiple dosing. For this reason, the study was performed in two parts, separated by a medication-free period of at least 7 days. In the single dose part, one tablet, containing 30 mg delapril and 2.5 mg indapamide, was administered to 12 male volunteers; in the multiple dose part, the volunteers received one tablet of the test preparation, once daily over 7 days. Following single and on the last day of the multiple dosing regimen, blood samples were withdrawn and serum concentrations of delapril and its metabolites M1, M2 and M3 and whole blood concentrations of indapamide were quantified by means of HPLC methods. In addition, urine samples were collected following single and multiple dosing for evaluation of the cumulative amount of delapril and its metabolites M1-M3 excreted in urine. For the area under the curve, calculated from time 0 to infinity (AUC(0-infinity)) the study revealed, following single dosing, mean values of delapril and its metabolites M1, M2 and M3 of 281, 2178, 739 and 716 h.ng/ml, respectively; for indapamide the mean value was 1597 h.ng/ml. The corresponding mean values found after multiple dose administration were 272, 2071, 857 and 598 h.ng/ml for delapril and its metabolites, respectively and 1536 h.ng/ml for indapamide. Evaluation of the cumulative amount of delapril and its metabolites M1-M3 excreted in urine (Ae) demonstrated mean values following single dosing (observation period 36 h) of 705, 4521, 454 and 4203 micrograms, respectively; the corresponding values after multiple dose administration (observation period 24 h) of the test preparation were 655, 4679, 469 and 4801 micrograms, respectively. The most important pharmacokinetic parameters AUC(0-infinity) and Ae were statistically compared by analysis of variance (ANOVA) and 90% confidence intervals were calculated. It may be concluded from the results of this study, that the bioavailability and pharmacokinetic parameters of the test preparation after single dosing and after multiple doses correspond well. The undesired side effects observed are known to occur after administration of the test preparation. The occurrence was a little more frequent after multiple dose application in comparison with the single dose administration.

Adult↗

PubMedDate not supplied

Topical nonsteroidal anti-inflammatory drugs in uncomplicated cataract surgery: effect of sodium naproxen.

PURPOSE: To investigate whether topical nonsteroidal antiinflammatory drugs (NSAIDs) are useful, in the absence of concomitant corticosteroid therapy, in limiting postoperative inflammation after uncomplicated cataract surgery. METHODS: A total of 328 patients were enrolled in a prospective, randomized, double-masked, parallel-group, active-controlled study. Anterior chamber inflammation (ACI) was evaluated as the primary efficacy parameter. Only patients with moderate inflammation (ACI score of < or =4) the day after surgery were randomized and treated with NSAIDs. A novel topical formulation containing 0.2% sodium naproxen was compared with 0.1% diclofenac. Both were administered three times a day for 14 consecutive days. Ocular inflammation was measured after 7 and 14 days by using slit-lamp biomicroscopy. Safety parameters were also evaluated at the same time. RESULTS: Both treatments were equally effective in controlling postsurgical inflammation. No statistically significant differences between treatment groups were observed for the safety variables. No serious adverse events (AEs) occurred during the course of the study. The most frequent AE reported with naproxen was eye redness. CONCLUSIONS: NSAIDs can effectively be used without concurrent administration of corticosteroids to control postoperative inflammation after uncomplicated cataract surgery. In addition, naproxen ophthalmic solution may be considered a suitable alternative to the currently available NSAIDs.

Administration, Topical↗