Search PubMed⌕ Search

Biomedical subjects

B Drewelow

Publications and source records attributed to B Drewelow.

31 records · Page 2Linked to original sources
PubMed1996

Rapid HPLC assay for verapamil and its metabolites: use for application to in vitro studies.

An improved method using isocratic reversed phase HPLC is presented for the extraction and rapid determination of verapamil and its main metabolites in microsomal preparations and cell culture media. Possibilities for using the method to estimate cytochrome P450 enzymes in microsomal test systems and hepatocyte cultures are described. The studies show that primary hepatocyte cultures are suitable for studying the metabolism and interactions of pharmaceuticals in vitro and could be superior to microsomal systems in many cases.

Biotransformation↗
PubMed1993

Generation of pharmacokinetic data during routine therapeutic drug monitoring: Bayesian approach vs. pharmacokinetic studies.

In three groups (each n = 12) of unselected hospitalized patients treated either with digoxin, theophylline, or gentamicin routinely performed TDM measurement of trough steady-state plasma levels (+ peak levels in case of gentamicin) was combined with a pharmacokinetic study at steady state (multiple blood sampling during one dosing interval). Pharmacokinetic parameters (apparent volume of distribution Vd, total plasma clearance CL) needed for individualization of dosage were evaluated by the Bayesian approach and a model-(in)dependent pharmacokinetic program (TOPFIT). Comparison of both methods revealed some small differences in the pharmacokinetic parameters for all three drugs. Mean deviations of the Bayesian estimates from the pharmacokinetic calculations of the three drugs ranged between 20 and 38% for Vd and between 13 and 22% for CL, indicating that the Bayesian approach provided reliable pharmacokinetic estimates for individualizing drug dosage under routine conditions. Therefore, it is suggested that routine TDM combined with Bayesian-based analyses can be regarded as an alternative to pharmacokinetic studies in clinically relevant populations.

Adult↗
PubMed1993

[Pancreas penetration by ofloxacin--a pilot study].

The use of antibiotics in patients with necrotizing pancreatitis is indicated since bacterial complications are the most common cause of death in this condition. Olfloxacin was studied in six patients regarding its permeation into pancreatic juice and bile and into pancreatic tissue in cases of chronic pancreatitis and pancreatic carcinoma. The peak concentrations in pancreatic juice (3.7 mg/l) and bile (12.9 mg/l) were found 20 minutes after i.v. administration of 3 mg/kg ofloxacin, these are 79 and 275% of the corresponding serum level, respectively. Pancreatic tissue concentrations varied between 54 and 333% of serum values in relation to the removal time of specimens and to the stage of inflammation. After three days and five days of ofloxacin treatment with doses of 2 x 200 mg daily even in pancreatic necroses concentrations were detected between 0.8 and 3.7 mg/kg wet weight. This suggests that in all pancreatic compartments analyzed, sufficient antibacterial ofloxacin levels above the MIC of relevant germs were found. Therefore, from a pharmacokinetic point of view, ofloxacin could be a potentially effective drug in prophylaxis and therapy of bacterial infections of the pancreas.

Adenocarcinoma, Mucinous↗
PubMed1991

[Pancreatic penetration of antibiotics].

Antibiotic therapy is indicated in acute pancreatitis because the most common complication and the mean reason for mortality is a bacterial infection. Concentrations of nine antibiotics from various classes were studied in the pancreatic tissue and pancreatic juice of patients and dogs. The volume of distribution is the most valuable parameter for predicting the potential pancreatic penetration of a substance. As a result of our pharmacokinetic studies mezlocillin and cefotiam, especially ciprofloxacin, have the most antiinfectious potential in treatment of acute pancreatitis. Metronidazole is suitable for combination in cases of pancreatic infections covering anaerobic bacteria.

Animals↗
PubMed1989

[Pancreatic kinetics of ampicillin].

Intravenous application of 50 mg/kg of ampicillin was followed by determination of ampicillin concentrations in surgically removed pancrease tissue of human patients and dogs. Concentration curves in pure pancreatic juice were recorded from dogs in which external pancreatic fistulae had been surgically induced. The ampicillin concentrations recorded from both human tissue and dogs were as low as six to eight per cent relative to corresponding serum levels. Values as low as 0.13 to 1.5 per cent relative to corresponding serum levels were recorded from pure pancreatic juice of dogs and from one human patient. These findings are likely to suggest that the permeation of ampicillin into the pancreas i too low and, consequently, cannot be effective for prophylaxis and therapy in the context of infectious complications.

Ampicillin↗
PubMed1988

[Effect of sulprostone on prolactin, HPL, HCG, progesterone and estradiol serum level in abortion induction in the first trimester in primigravidae].

The influence of the i.m. application of Sulproston for induction of abortion was examined on the serum levels of PRL, HCG, HPL, estradiol and progesterone in 8 primigravidae during the first trimenon. The hormones were determined by RIA. There was a drop of HCG, HPL, estradiol and progesterone beginning 4 to 16 hours after the first application of Sulproston. PRL was not influenced.

Abortifacient Agents↗
PubMed1987

[Experiences with the use of sulprostone (Nalador) for the termination of pregnancy in the 1st trimester in primigravidae].

Sulprostone in different doses and application forms (25, 50 or 100 micrograms extra-amnionic; 500 micrograms or 3 times 500 micrograms every 4 hours intramuscularly) was given to perform termination of pregnancy between 7th and 12th week. The dose of 500 micrograms three times given was most effectiveness, but there were the most side effects, too. The dose of 500 micrograms Sulproston was accompanied by less side effects and the therapeutic success was sufficient. The extra-amnionic application was effective also in all used dosages.

Abortifacient Agents↗
PubMedDate not supplied

Penetration of ceftazidime into human pancreas.

The use of antibiotics in patients with severe acute pancreatitis (stage II and III) is indicated since bacterial complications are the most common cause of death in these patients. In the present study the penetration of ceftazidime into pancreatic juice, into healthy and chronically inflamed pancreatic tissue as well as into necrotic regions in cases of severe acute pancreatitis was investigated. A peak concentration of 12.9 +/- 5.9 mg/l was found 60 min after intravenous administration of 35 mg/kg of the drug, which is 32% of the corresponding serum levels. Pancreatic tissue concentrations varied between 9 and 79% of the corresponding serum levels, depending on the stage of inflammation. After five days of antibiotic treatment with doses of 2 g t.i.d., concentrations between 1.8 and 6.9 mg/kg were detected even in pancreatic necroses. This suggests that sufficient antibacterial levels of ceftazidime were present in all pancreatic compartments analyzed following administration of common therapeutic dosages. Therefore, from a pharmacokinetic point of view, ceftazidime could be a potentially effective drug for the treatment of pancreatitis.

Acute Disease↗
PubMedDate not supplied

Primary or established liver cells for a hybrid liver? Comparison of metabolic features.

It is currently in discussion whether or not established liver cell lines can be used for an extracorporeal liver assist device. Thus, metabolic features of primary hepatocytes, immortalized hepatocytes, and hepatoma cells were compared. The ability of these cells to process toxic blood of patients with hepatic failure was investigated by testing their viability in toxin enriched medium that was obtained by toxin separation from patients' blood via a molecular adsorbents recirculating system (MARS). In addition, glucose metabolism, urea synthesis, P450 dependent verapamil metabolism using high performance liquid chromatography, and interleukin-6 induced "acute phase" reaction by sulfodesoxysalicylic acid-polyacrylamide gel electrophoresis detected changes of albumin synthesis were determined in primary hepatocytes and in established liver cells. The viability of hepatoma cells after contact with the toxic compounds coming from the patients' blood was significantly decreased in comparison to that of immortalized hepatocytes and primary hepatocytes. Immortalized hepatocytes and hepatoma cells showed a significantly higher consumption of glucose associated with a significantly higher lactate synthesis. A basic urea synthesis rate could be measured in immortalized hepatocytes and hepatoma cells, but it was significantly lower than that of primary cells. P450 with its subenzyme CYP2C was inducible only in primary hepatocytes and in immortalized cells, but in the latter the enzymatic activity was lower than that of primary cells. The incubation with acute phase mediators resulted in a decrease of albumin synthesis in primary hepatocytes and in hepatoma cells, but it increased the albumin synthesis in immortalized hepatocytes. Summarizing these data, partially beneficial effects can be assumed if established cells are used in an extracorporeal liver assist device. These might include synthesis of some compounds and basic metabolic activities, such as urea synthesis. However, established liver cells showed clearly altered metabolic characteristics. The sufficient removal of toxic compounds requires additional strategies for detoxification by primary hepatocytes in sufficient amounts.

Acute-Phase Reaction↗