Biomedical subjects

T Zimmermann

Publications and source records attributed to T Zimmermann.

At least 109 records · Page 6Linked to original sources

PubMed1995

Comparative pharmacokinetics of fluconazole and of itraconazole in Japanese and in German subjects.

In separate but identically designed studies the oral pharmacokinetics of 100 mg doses of the 2 antimycotics fluconazole and itraconazole were examined in Japanese and German subjects (both n = 12), both fasting and concomitant to a heavy breakfast. The results with the 2 races were compared. With fasting subjects no significant difference was found with either antimycotic for any parameter. With fluconazole the pharmacokinetic parameters after food were essentially the same for the 2 races. The only significant difference, a delay of 1.5 h in the median tmax in the Japanese relative to the Germans, should not be of practical importance. In contrast, the mean AUC for itraconazole in Japanese subjects after the meal was only 54.9% of the value with Germans (p < 0.05); the corresponding Cmax was only 54.7% (p < 0.01). As itraconazole is normally administered together with food, this suggests that there is a possibility of underdosage in Japanese subjects. There appears to be no such problem with fluconazole.

Administration, Oral↗

PubMed1995

[Congenital tracheoesophageal fistula in the adult].

Congenital esophago-tracheal and esophago-bronchial fistulae are rare. Symptoms are recurrent pneumonia, cough, dysphagia and pain. The diagnosis is made by bronchoscopy or esophagoscopy. Every time the diagnosis is certain, the fistula has to be exstirpated by means of a thoracotomy and plastic reconstructive flap surgery.

Adult↗

PubMed1995

Pharmacokinetic optimization of the treatment of oral candidiasis with fluconazole: studies with a suspension.

An open crossover study was performed in 12 healthy subjects to investigate the pharmacokinetics in saliva and plasma of a 100 mg oral dose of fluconazole, administered as either a capsule or as a suspension, the latter being used to rinse the mouth and retained for 2 min before being swallowed. In terms of fluconazole plasma concentrations the capsule and the suspension were essentially bioequivalent. While the saliva concentrations of fluconazole after capsule administration reached their peak at 3.0 +/- 0.8 micrograms/ml 4 h after dosage, administration of the suspension resulted in a mean peak concentration of 551.1 +/- 425.6 micrograms/ml 5 min after ingestion. The saliva concentrations decreased gradually after ingestion of the suspension, but were higher for 4 h than the corresponding levels from the capsule. The area under the curve (AUC) from 0 to 96 h of fluconazole in saliva was 227.7 +/- 73.8 h micrograms/ml after the suspension, compared to 123.5 +/- 25.5 h micrograms/ml after the capsule, indicating that the total drug exposure to the oral mucosa by the salivary route was enhanced more than 80% with use of the suspension. Four h after administration of the suspension, saliva and plasma concentrations of fluconazole were in equilibrium, at a saliva: plasma ratio of around 1.2. Taken together, the present results suggest that the treatment of oral candidiasis with fluconazole may be optimized by use of an oral suspension, as this delivers pharmacologically active levels of the drug to the site of infection by both topical and systemic routes.

Adult↗

PubMed1995

Prediction of phenotype for dextromethorphan O-demethylation by using polymerase chain reaction in healthy volunteers.

The polymorphism of dextromethorphan (CAS 125-71-3) metabolism is dependent on hepatic cytochrom P4502D6 (CYP2D6) activity. The relationship between the CYP2D6 genotype and the dextromethorphan phenotype was studied in 83 healthy unrelated subjects. Genotype was determined by allele-specific polymerase chain reaction (PCR). Phenotyping was performed by administration of 25 mg dextromethorphan hydrobromide and determination of the urinary metabolic ratio of dextromethorphan and its O-demethylated metabolite dextrorphan (DEM/DOR). Six subjects (7.2%) were homozygous for mutant alleles (95% confidence interval 2.7%-14.7%), 18 subjects (22%) were heterozygous carriers, and 59 were homozygous for the wild-type allele. Six subjects were classified as poor metabolizers (PM) of dextromethorphan, 77 as extensive metabolizers (EM). Genotyping correctly predicted all PMs and EMs. The CYP2D6-B mutation was most frequently found, being present in 83% of PM and 8% of EM alleles. Heterozygous EMs (22% of the total population studied) were significantly underrepresented compared to the expected genotype frequency of 31% (p < 0.05). The extensive metabolizers who were heterozygous for the wild-type allele had a significantly higher metabolic ratio, compared to the homozygous EMs (log10DEM/DOR [95% = -1.99 [(-2.30)-(-1.69)] vs. -2.55 [(-2.67)-(-2.43)]; p < 0.001), indicating a gene-dose effect for CYP2D6.

Adult↗

PubMed1995

[The relative bioavailability and pharmacokinetics of standardized myrtol].

An open, randomized cross-over trial was performed in 20 healthy volunteers to evaluate the relative bioavailability and the pharmacokinetics of myrtol standardized, the active ingredient of Gelomyrtol and Gelomyrtole forte capsules (abbreviated as GE and GF, respectively, in the following text). The male subjects, aged 19 to 42 years, were given in a randomized manner 1 capsule of GE (120 mg myrtol stand.) uncrushed, 1 capsule of GE crushed, 1 capsule of GF (300 mg myrtol stand.) uncrushed and 1 capsule of GF crushed on 4 different days. The time of administration was always about 8 a.m. and the medication had to be swallowed with 200 ml water. The 4 study sessions were separated (correction of spearated] by at [correction of a] least 6 days. Prior to and 15, 30, 45, 60, 75, 120, 150 min and 3, 4, 5, 8, 12 and 24 h after medication at least 10 ml blood were taken from an antecubital vein. The blood samples were centrifuged within 20 min, the plasma was separated, and transferred into tubes and immediately deep-frozen at -20 degrees centigrade. From GE capsules cineol as main component was absorbed to 93,2% and from GF capsules to 95,6% based on the comparison of the uncrushed with the crushed capsules. The geometric mean of Cmax was 72,4 ng/ml for GE uncrushed capsules, a value of 33% below that for the crushed ones. The time to peak (tmax) was three times higher. With GF Cmax reached 238,2 ng/ml for the uncrushed capsules, a value of 36% below the one for the crushed ones and tmax was 67% higher. The time until the appearance of measurable plasma concentrations (tlag) was 7 and 5 times higher, respectively. These results show, that the main components of myrtol standardized, the active ingredient of GE and GF, are absorbed about 100% compared to the liquid form of administration (crushed capsule). The enteric coating of the capsules produces lower plasma peak-concentrations at later time points. This results in a plateau-like phase of the concentration/time curve between the 2nd and the 8th hour after application and reveals a considerable therapeutic advantage of the enteric coating.

Adult↗

PubMed1994

[Mental performance after administration of chloral hydrate. Evaluation of hangover with clinical dose within the scope of a placebo controlled double-blind study].

PROBLEM: Many hypnotic drugs are associated with hangover effects that impair performance thus compromising safety, e.g. in road traffic. METHOD: To investigate this phenomenon, a daily dose of 1,000 mg (2 capsules of 500 mg) was given to twenty healthy men and women (mean age 44.1 +/- 8.6 years) over a period of six days. The test subjects were examined prior to treatment, 1 hour after the first dose of 1,000 mg and in morning and afternoon of the day following the 1st, 3rd and 6th evening doses. A second group of equal number and equal size received placebo and served as controls. Medication was given in a randomized, double-blind manner. PARAMETERS: Seven items of performance were examined (including reaction ability, concentration and vigilance) together with state of well-being and adverse reactions. RESULTS: As expected of a hypnotic drug, the acute effect of chloral hydrate included a number of disturbances of performance (in particular processing of information) and well-being. However, when chloral hydrate was taken in the evening as intended, the test subjects were able to concentrate better the next day, and were calmer and more balanced.

Adult↗

PubMed1994

Influence of concomitant food intake on the oral absorption of two triazole antifungal agents, itraconazole and fluconazole.

The influence of food on the pharmacokinetics of the triazole antimycotics fluconazole and itraconazole was investigated in a randomised, parallel group, single dose study in 24 healthy subjects. Each group took either a 100 mg capsule of fluconazole or a 100 mg capsule of itraconazole, pre-prandially or after a light meal or a full meal, in a three-way crossover design. Gastric and intestinal pH were measured with a co-administered radiotelemetric pH capsule, and gastric emptying time of the capsule (GET) was taken as the maximum gastric residence time of drug and food. The plasma AUC and Cmax of itraconazole were significantly different under the various conditions and the mean AUC was greatest after the full meal. The bioavailability (90% confidence intervals) of itraconazole relative to that after the full meal, was 54% (41-77%) on an empty stomach and 86% (65-102%) after a light meal. The criteria for bioequivalence were not attained. In contrast, the bioavailability (90% CI) of fluconazole relative to the full meal was 110% pre-prandially (100-115%) and 102% after the light meal (88-103%), and the criteria for bioequivalence were attained. Itraconazole absorption was promoted by low stomach pH, long gastric retention time and a high fat content of the coadministered meal, whereas the pharmacokinetics of fluconazole was relatively insensitive to physiological changes in the gastrointestinal tract.

Administration, Oral↗

PubMed1994

Interactions between malignant tumor growth and allogeneic graft rejection in an experimental rat model.

We describe a combined tumor and simultaneous transplant model in rats in tended to investigate interactions between tumor growth and graft rejection. To study the influence of tumor growth on graft rejection. Novikoff hepatoma cells were injected subcutaneously into the back of Lewis rats. Eight days later, the grown solid tumor was resected, and allogeneic heart transplantation was performed. Four groups were formed, receiving 5-fluorouracil (5-FU), cyclosporin A (CsA), 5-FU + CsA, and placebo, respectively. In the corresponding groups, tumor injection was omitted. Graft survival was significantly prolonged when CsA was given 5-FU did not abrogate or augment CsA efficiency nor influence graft survival when given alone. In the corresponding control groups, graft survival was similar, thus excluding an immunomodulating effect of the prior tumor growth on graft survival. To study the reverse interaction of allogeneic graft on tumor growth, heart grafting and tumor cell injection were performed on the same day. In different groups, 5-FU, CsA, 5-FU + CsA, and placebo was given. For the control, no transplantation was carried out. The tumor was resected on the 8th postoperative day and examined by immunohistology. A slight decrease of tumor growth by 5-FU, but a marked increase by CsA were found, whereas the graft alone showed no immunomodulation.

Animals↗

PubMed1994

[Malignant tumors of the small intestine].

In a retrospective analysis, we studied 24 cases of malignant small bowel tumors. Apart from 9 cases of a carcinoid tumor, there occurred 6 cases of leiomyosarcoma and another 7 cases of adenocarcinoma. One case of malignant schwannoma and another case of lymphoma were also seen. Sonography and contrast-study of the GI-tract were the decisive diagnostic tools. Nevertheless, months and even years elapsed before diagnosis was established. Only in 13 patients curative resection could be accomplished. In the remainder of patients, hepatic metastases were found or the tumor could not be resected any more owing to its size. In 6 patients with synchronous and in 7 patients with metachronous liver metastases we carried out palliative regional intraarterial chemotherapy of the liver. The mean survival time of the whole patient group was 19 months. Patients, having submitted themselves to a complete resection of the tumor, had a significantly longer period of survival (mean survival time 25 months) in contrast to patients, having undergone a mere palliative operative procedure (mean survival time 14 months). Mean survival time for leiomyosarcoma was 38 months, for adenocarcinoma 14 months, and for carcinoid tumors 22 months. Owing to difficulties in establishing diagnosis, a tumor of the small intestine should be considered in any patient complaining of abdominal pain.

Adenocarcinoma↗

PubMed1994

The influence of gastric pH on the pharmacokinetics of fluconazole: the effect of omeprazole.

AIDS patients may have achlorhydria, a condition that could result in drug malabsorption, especially of antifungals. The effect of a reduction in the production of gastric acid on the pharmacokinetics of the antimycotic fluconazole after a single 100 mg dose was investigated in a randomized two-way crossover study with 12 healthy volunteers. Gastric acid production was reduced by pretreatment with 20 mg omeprazole/day over a period of 7 days; pH and gastric emptying times were measured by a radiotelemetering pH capsule. Omeprazole pretreatment significantly raised the median gastric pH (from pH 1.1 to pH 4.7, p < 0.0001), but had no significant influence on gastric emptying time of the pH capsule (median = 4.3 vs 4.9 hours). The pharmacokinetics of fluconazole were unchanged; plasma parameters were Cmax = 2.04 micrograms/ml, tmax = 4.08 h and AUC = 98.91 h micrograms/ml after the omeprazole treatment, compared to 2.06 microliters/ml, 3.92 hours and 97.29 h micrograms/ml, respectively. The median bioavailability ratio of fluconazole before and after omeprazole treatment was 1.00. It is inferred that there is no interference of omeprazole with the plasma pharmacokinetics of fluconazole. The findings suggest that changes in gastric pH, as in patients with AIDS or those being treated with anti-ulcer drugs, should not influence the pharmacokinetics of fluconazole.

Administration, Oral↗

PubMed1994

[Surgical treatment of tracheal injuries].

Traumatic and iatrogenic injuries of the trachea are rare. In case of suspected rupture of the trachea a bronchoscopy remains the 'gold standard' of diagnostic procedures. The injuries should be repaired as soon as possible through a right thoracotomy or a collar incision using resorbable sutures. In case of small lesions a conservative treatment may be discussed. Overall the prognosis of tracheal injuries is good.

Adult↗

PubMed1994

Influence of concomitant food intake on the gastrointestinal absorption of fluconazole and itraconazole in Japanese subjects.

The effect of food intake on the pharmacokinetics of orally administered fluconazole or itraconazole was investigated in a single-dose randomized two-way crossover study in Japanese subjects. 100-mg capsules of fluconazole or itraconazole were given to two parallel groups, each of 12 male and female volunteer subjects, and plasma concentrations of the antimycotics were determined by specific assays. Gastric pH and gastric emptying times were measured by coadministration of a radiotelemetric pH capsule. Intersubject variations in drug plasma concentrations were found to be much higher with itraconazole than with fluconazole. The coefficient of variation of the AUC (0-72) after food amounted to +/- 62% for itraconazole and +/- 16% for fluconazole. The consumption of a heavy breakfast significantly delayed the tmax of both drugs by approximately two hours (p < 0.05). This effect was accompanied by a significant prolongation of gastric emptying times (p < 0.0001). Food intake had essentially no effect on the absorbed amounts of fluconazole. The median relative bioavailability (postprandial vs fasting) based on AUC (0-72) was f = 0.99, with an individual range from 0.72 to 1.15. The corresponding Cmax ratio was 1.04 (range 0.91-1.17). The effect of food on the bioavailability of itraconazole was highly variable: it ranged from marked reductions (f = 0.35) to large increases (f = 3.74) of the AUC (0-72), at a median ratio of f = 1.23. The Cmax ratios postprandial vs fasting ranged between 0.27 and 5.71 (median = 1.04). It is concluded that food had an unpredictable effect on the extent of itraconazole absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1994

Distribution of orally administered azithromycin in various blood compartments.

The concentrations of azithromycin in whole blood, plasma, erythrocytes and polymorphonuclear leucocytes (PMNLs) were measured in 6 healthy volunteers following the last administration of a three-day regimen of 500 mg once daily. Marked enrichment of azithromycin was observed in PMNLs; the drug concentration amounted to 119 +/- 31 (SD) mg/l 6 hours after the administration. Twelve days thereafter 42 +/- 10 mg/l azithromycin was still measured in the PMNLs, although the drug was no longer demonstrable in plasma (< 0.02 mg/l). The elimination of azithromycin from the PMNLs (half-life 210 +/- 69 hours) was clearly slower than the elimination from plasma (half-life 93 +/- 70 hours). The maximal concentrations of azithromycin in plasma (0.64 +/- 0.27 mg/l) and erythrocytes (0.17 +/- 0.06 mg/l) were much lower and occurred earlier (tmax = 3 hours) than those observed in the PMNLs. The enrichment factor for azithromycin in PMNLs relative to plasma came to 177 +/- 92 at 3 hours or 1814 +/- 706 at 120 hours after the last administration. In a parallel in vitro study, the effect of accumulation of azithromycin in PMNLs on the intracellular survival of ingested staphylococci was investigated. At subinhibitory extracellular concentrations of azithromycin as low as 0.03 mg/l (MIC = 1 mg/l), a significant reduction in bacterial viability was observed, thus demonstrating antibacterial activity of the intracellularly enriched antibiotic.

Administration, Oral↗

PubMed1994

Pharmacological comparison of the stereoisomers of glyceryl-1-nitrate.

The enantiomers of glyceryl-1-nitrate, a metabolite of glyceryl trinitrate, were pharmacologically characterized in vitro and in animals. In the Langendorff heart (l) G-1-N was double as potent as (d) G-1-N with respect to the enhancement of coronary flow. The two enantiomers showed almost the same dose-response curves in rabbit aortic strips contracted with phenylephrine. In the same model there were no enantiospecific differences in the development of cross-tolerance to glyceryl-trinitrate. In anaesthetized rabbits, intravenous (l) G-1-N reduced the blood pressure slightly more than (d) G-1-N, while in the conscious dog the blood pressure lowering effect of (d) G-1-N was greater and had a much longer duration (4-6 versus 2 h) than that of (l)G-1-N. The differences in dogs are probably explained by enantiospecific pharmacokinetics: (d) G-1-N had higher plasma levels and showed a longer half-life of elimination than (l) G-1-N (more than 5 h versus 2.7 h). Both enantiomers enhanced the rate of survival after acute coronary ligature in rats with a tendency to higher long-term survival rates after the (d) form.

Administration, Oral↗

PubMed1994

[Pharmacodynamic equivalence and clinical trial of a new fluorocarbon-free glycerol trinitrate pump spray with low ethanol content in comparison to a fluorocarbon-containing reference spray and a fluorocarbon-free pump spray with high ethanol content].

The pharmacodynamic equivalence of a fluorohydrocarbons-(FCH)-free glyceryl trinitrate (GTN, CAS 55-63-0)-containing pump spray with low ethanol content (Nitrolingual-Spray N; TL) versus a conventional FCH-containing GTN spray (Nitrolingual-Spray, R) as reference and a FCH-free GTN pump spray with high ethanol content (TH) was investigated by digital plethysmography (DPG) in a double-blinded, placebo-controlled (TL-matched placebo spray), randomized, period-balanced, 4-way cross-over design. Additionally the clinical tolerability (as perceived by the subjects and reported to the treatments-administrating investigator) was determined. The DPG-changes (cla; ratio of c-incisure and systolic a-wave) after the sublingual (s.l.) administration of 0.8 mg GTN of TL were biostatistically equivalent with R: the confidence intervals (CI) of the point estimates of the maximal decrease in cla (TL/R: 0.98, 90%-CI: 0.84 to 1.14) and the area-weighted average decrease in cla (TL/R: 0.97, 90%-CI: 0.80-1.16) were well in a 80-125% tolerance range. The time of occurrence of the maximal DPG-effect of TL was not different from R (distribution-free estimate of the difference TL-R: -2.25 min, 95%-CI: -9.5 min to 2 min). In contrast the maximal DPG-effect of TH after the s.l. administration of 0.8 mg GTN had a statistically significant earlier onset (TH-R: -6 min, 95%-CI: -9.5 min to -2 min) and a higher area-weighted average response (TH/R: 1.12, 90%-CI: 0.95 to 1.34). TH consistently caused an utterly unpleasant burning sensation in the mouth, thus this perceived local discomfort was distinctly different compared to all other treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Sublingual↗

PubMed1993

[Palliative therapy of primary liver tumors].

In Europe and North America, primary liver tumors are rare. Resection is the only means of cure, but is possible in only 20-30% of the patients affected, so that in all other patients, i.e. the vast majority, only palliative treatment is possible. In a retrospective analysis we investigated the 68 patients we had treated for hepatocellular or cholangiocellular carcinoma of the liver. In 14 patients resection was possible, while 28 patients were treated by chemoembolization and 26 by intraarterial regional chemotherapy to the liver. There was no difference in tumor stage between the two groups receiving different palliative treatments. The patients in whom resection was performed, in contrast, mostly had less advanced tumors. For chemoembolization we used a mixture of Ethibloc, mitomycin, Adriamycin and cisplatin. Up to 1986, the intraarterial chemotherapy was performed with mitomycin and 5-FU. Since 1986 we have used Adriamycin and cisplatin. The overall median survival time was 8 months: after resection 17 months, after chemoembolization 6.5 months, and after intraarterial chemotherapy 6.5 months. There was a significant difference in survival between patients with tumor stage II and those with tumor stages III and IV. On comparing the survival time achieved with our treatments and that ensuing in the natural course of patients with liver tumor we found no improvement.

Adenoma, Bile Duct↗

PubMed1993

[Effect of perioperative donor blood transfusion on prognosis of bronchial cancer].

Immunological research and experimental animal studies have shown that allogeneic blood has an immunosuppressive effect. Several clinical investigations have demonstrated the negative influence of blood transfusions on the prognosis after curative resection of colorectal carcinoma. However, there are only a few studies about the influence after complete removal of lung cancer, and the results are contradictory. In our retrospective study we analyzed the follow-up results of 224 patients (192 men, 32 women; average age 57 years) on whom we had performed a curative resection of their bronchogenic carcinoma. A total of 119 patients had received nonspecific random blood transfusions. The survival rate for patients with blood transfusions was significantly worse in comparison to the non-transfused group 2 years after the operation (74% vs 59%, P = 0.019); after 5 years, however, no difference could be seen (43% vs 43%). Even when we subdivided our patients according to tumor cell type, tumor stage, differentiation and method of resection, the negative influence of transfused blood was confirmed for the 2-year survival rate, but again had disappeared 5 years after the operation.

Adult↗

PubMed1993

[Pancreatic pseudocysts after blunt abdominal trauma].

Pancreatic pseudocyst caused by trauma is rare. Only in 5 of 98 patients on whom we operated between 1977 and 1991 for pancreatic pseudocyst were we able to detect previous blunt abdominal trauma. In a 4-year-old girl just a slight abdominal trauma had given rise to a cyst, while in 2 other patients (aged 9 and 26 years) pancreatitis occurred after trauma that was treated medically. Two patients had to undergo laparotomy immediately after suffering serious abdominal blunt injury. Diagnosis was established sonographically, except in one case, in which a large cyst was determined to originate from the pancreas, but only intraoperatively. The time-span between trauma and treatment of the pseudocyst ranged from 3 months to 1 year. Thus, continuous percutaneous suction, which is basically considered a promising therapy for cysts in their early stages of development, was obviously not feasible in our patients. We therefore carried out cysto-jejunostomy with formation of a Roux-en-Y jejunum loop. At follow up 1-10 years after operation, all patients were asymptomatic and no cyst formation could be detected sonographically.

Abdominal Injuries↗