Biomedical subjects

P Koeppe

Publications and source records attributed to P Koeppe.

At least 19 recordsLinked to original sources

PubMed1992

Pharmacokinetics of loracarbef and interaction with acetylcysteine.

A study was conducted to evaluate the pharmacokinetics of loracarbef, a new synthetic oral carbacephem antibiotic, following administration of 400 mg in normal male volunteers. The influence of food and possible interaction with acetylcysteine, a commonly used mucolytic agent, was also studied. Twelve healthy volunteers participated in the study and randomly received an oral dose of 400 mg loracarbef in the fasting state, 400 mg loracarbef following a standard breakfast or 400 mg loracarbef together with 200 mg acetylcysteine in granular form. Serum and urine concentrations were determined over 24 h by means of a bioassay. Loracarbef was well tolerated. Four volunteers complained of mild, transient headache. The substance was well absorbed with a mean peak level of 19.21 +/- 3.94 mg/l in the fasting state; it was primarily excreted in active form via the kidneys (urine recovery/24 h: 86-92%). The elimination half-life ranged from 70.3 to 102.0 min. Acetylcysteine had no effect on the absorption of loracarbef. The intake together with food delayed the absorption time, but had no influence on the bioavailability.

Acetylcysteine↗

PubMed1992

Pharmacokinetics of roxithromycin and influence of H2-blockers and antacids on gastrointestinal absorption.

The pharmacokinetics of roxithromycin (300 mg orally) and the influence of the antacid aluminum magnesium hydroxide and the H2-blocker ranitidine on bioavailability of roxithromycin in ten healthy volunteers were studied. Pharmacokinetics after a single dose of roxithromycin were characterized by high peak serum levels (9.1 +/- 2.1 mg/l) and a long elimination half-life (7.2 +/- 2.5 h), resulting in a large area under the curve (116.9 +/- 32.7 mg h/l). High inter- and intraindividual variations were found for both the absorption time and the elimination half-life. The bioavailability of roxithromycin was not affected by coadministration with antacids or ranitidine.

Adult↗

PubMed1992

Multiple dose pharmacokinetics, safety, and effects on faecal microflora, of cefepime in healthy volunteers.

In a randomized, double-blind, placebo-controlled study in 12 healthy volunteers pharmacokinetics, safety and impact on the faecal microflora of cefepime were determined. For eight days eight volunteers received cefepime 1000 mg bd by constant infusion over 30 min, four volunteers received placebo. Concentrations of cefepime in serum and urine were measured by bioassay and HPLC. The correlation between the two methods was good and the bioassay results were used for pharmacokinetic calculations. The faecal flora was analysed twice before the study, twice during the study and four times after cefepime administration. There were no significant differences in the pharmacokinetic parameters between days 1 and 8. The following values (mean +/- S.D.) represent day 1. The maximum concentration of 72.69 +/- 12.2 mg/L immediately after infusion decreased to 0.56 +/- 0.17 mg/L after 12 h. The mean 12 h recovery in urine was 93.69 +/- 2.14%. Pharmacokinetic parameters based on an open two-compartment model were as follows (mean +/- S.D.): area under the curve, 142.65 +/- 18.35 mg.h/L; elimination half-life 110.3 +/- 8.3 min; steady state volume of distribution 16.0 +/- 1.9 L/70 kg; total clearance, 107.0 +/- 16.0 mL/min; renal clearance 103.0 +/- 15.2 mL/min. No accumulation was observed during the eight day study period with cefepime at this dosage; trough levels on days 2-7 ranged from 0.52 +/- 0.26 mg/L to 0.90 +/- 0.33 mg/L. In the cefepime treated group the following side-effects were noted: headache (5), fatigue (4), nausea/stomach ache (2), soft stool (2), transient scotoma (1). Side-effects in the placebo group were: headache (2) fatigue (3), nausea/stomach-ache (1), soft stool (2) and photophobia (1). During cefepime administration a decrease in the number of Escherichia coli and bifidobacteria in faeces was observed, whereas Bacteroides spp. and clostridia showed a slight increase. The numbers of faecal bacteria returned to normal 20 to 48 days after the study was completed.

Bacteroides↗

PubMed1992

Multiple-dose pharmacokinetics of cefprozil and its impact on intestinal flora of volunteers.

The pharmacokinetics of cefprozil were determined with 12 volunteers (8 received cefprozil and 4 received a placebo) after oral administration of 500 mg every 12 h over an 8-day period in a randomized, double-blind, placebo-controlled design. Concentrations in serum and urine were measured by high-pressure liquid chromatography and bioassay. The pharmacokinetic parameters were calculated on the basis of an open one-compartment model. The mean maximum concentration in serum on day 1 was 11.5 +/- 2.6 mg/liter, and the time to reach maximum concentration was 122.3 +/- 30 min after administration. Bioavailability parameters (area under the concentration-time curve from zero to infinity, maximum concentration of the drug in serum, and urinary recovery) indicated an excellent absorption. No accumulation over the 8-day period was registered. Cefprozil had a short biological elimination half-life of 58 +/- 10 min and a renal clearance of 210 +/- 51 ml/min, indicating high rates of renal excretion and tubular secretion. Analysis of the fecal flora showed an ecological impact of cefprozil on the intestinal microflora, such as a moderate decrease in enterobacteria and a slight increase in enterococci, staphylococci, and bacteroides during the study. The number of all bacterial species was already normalized 4 days after the administration period. The tolerance of cefprozil proved to be excellent; only a slight and reversible increase of liver enzymes (in two volunteers), mild cephalalgia, tiredness, and soft stool were registered during the 8-day period. Cefprozil had excellent absorption, no accumulation over an 8-day period, and only a limited impact on the intestinal microflora.

Administration, Oral↗

PubMed1992

Pharmacokinetics of cefpodoxime proxetil and interactions with an antacid and an H2 receptor antagonist.

Cefpodoxime proxetil is a new oral esterified cephem antibiotic with a broad antibacterial spectrum. The dissolution of cefpodoxime proxetil is pH dependent. The objectives of this study were to characterize the pharmacokinetics of cefpodoxime proxetil in two different oral doses and to examine possible interactions with an antacid, aluminum magnesium hydroxide (Maalox 70), and an H2 receptor antagonist, famotidine. Two studies involving the same 10 healthy volunteers were performed. In the first study, cefpodoxime proxetil was administered in two doses, 0.1 and 0.2 g. In the second study, two interventions were performed in a randomized crossover design. For one intervention, the volunteers were pretreated with 40 mg of famotidine 1 h before 0.2 g of cefpodoxime proxetil was administered. In the second trial, participants were given 10 ml of Maalox 70 2 h and 10 ml of Maalox 70 15 min before they received 0.2 g of cefpodoxime proxetil. Serum and urine concentrations were determined by high-performance liquid chromatography. For the statistical evaluation, these data were tested by using the pharmacokinetics of 0.2 g of cefpodoxime proxetil from the first study. The maximum concentrations were 1.19 +/- 0.32 mg/liter after 0.1 g of cefpodoxime proxetil and 2.54 +/- 0.64 mg/liter after 0.2 g of cefpodoxime proxetil. The elimination half-lives were 149 min for 0.1 g and 172 min for 0.2 g of cefpodoxime proxetil. The total increase in the area under the concentration-time curve (AUC) was dose dependent. Combination with Maalox 70 caused a reduction in the AUC from 14.0 +/- 3.9 to 8.44 +/- 1.85 mg.h/liter. After famotidine, the AUC decreased to 8.36 +/- 2.0 mg . h/liter. Corresponding changes were registered for the maximum concentration of drug in serum, 24-h urine recovery, and the time to maximum concentration of drug serum. Cefpodoxime proxetil was well tolerated without any seriously adverse drug reactions.

Administration, Oral↗

PubMed1990

Quinolone pharmacokinetics and metabolism.

The pharmacokinetic properties of the new fluoroquinolones are characterized by a high volume of distribution, long biological half-life, low serum protein binding, elimination by renal and extrarenal mechanisms with high total and renal clearances, limited biotransformation and moderate to excellent bioavailability after oral administration. However, each quinolone derivative (ciprofloxacin, enoxacin, fleroxacin, norfloxacin, ofloxacin and pefloxacin) possesses individual pharmacokinetic parameters, which should be considered in the treatment of patients, especially when liver or renal dysfunction exists.

Administration, Oral↗

PubMed1990

Concentrations of ofloxacin in human bone and in cartilage.

Concentrations of ofloxacin were determined in bone, cartilage and serum of 23 patients (8 male, 15 female; age 29-85 years) who underwent total hip replacement for osteoarthritis. A single dose of 200 mg ofloxacin was infused over a period of 20 min. Blood specimens (total 89), bone (45), and cartilage specimens were taken up to 720 min after the infusion. Ofloxacin was determined by high performance liquid chromatography. Bone was extracted with buffer three times to obtain a complete extraction. An average bone density of 1.9 kg/l was assumed in order to convert concentrations from mg/kg to mg/l bone. Mean serum concentrations decreased from 7.2 +/- 2.6 (0 min) to 0.5 +/- 0.1 (720 min). Mean tissue concentrations (mg/l) at 98, 246 and 716 min after the end of infusion were, in cortical bone 0.64 +/- 0.29, 0.86 +/- 0.55 and 0.59 +/- 0.14; in cancellous bone, 1.70 +/- 0.72, 1.47 +/- 1.00 and 0.99 +/- 0.43, and in cartilage 1.38 +/- 1.05; 2.19 +/- 1.56 and 2.18 +/- 0.45. The half-life of ofloxacin in tissues was longer than in serum. No side effects were observed.

Adult↗

PubMed1990

Pharmacokinetics and serum bactericidal activities of quinolones in combination with clindamycin, metronidazole, and ornidazole.

To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram-positive bacteria, we investigated in two studies the parenteral combinations of ciprofloxacin (200 mg) and ofloxacin (200 mg) with metronidazole (500 mg) or clindamycin (600 mg) and the oral combinations of enoxacin (400 mg) and fleroxacin (400 mg) with metronidazole (400 mg), clindamycin (300 mg), or ornidazole (500 mg) (only with fleroxacin). The pharmacokinetics and serum bactericidal activities (SBAs) against 5 aerobic and 2 anaerobic species (total, 58 strains) were determined in two groups of 10 healthy volunteers by using a randomized crossover study design. The additions of metronidazole, clindamycin, and ornidazole did not affect the pharmacokinetics of the quinolones. The combination of clindamycin with ciprofloxacin, ofloxacin, and, to a lesser extent, fleroxacin resulted in an increase of the SBA against gram-positive strains (mean peak titers): Staphylococcus aureus, ciprofloxacin alone, 1:5.5; ciprofloxacin-clindamycin, 1:19.9; ofloxacin alone, 1:3.6; ofloxacin-clindamycin, 1:17.5; fleroxacin alone, 1:4.3; fleroxacin-clindamycin, 1:8.1; Streptococcus pneumoniae (fleroxacin and enoxacin were not tested), ciprofloxacin alone, 1:2.0; ciprofloxacin-clindamycin, 1:53; ofloxacin alone, 1:2.6; and ofloxacin-clindamycin, 1:49.2. The high SBA of quinolones against gram-negative bacteria was not affected by the combinations; however, relatively low activities against Pseudomonas aeruginosa were detected. In general, against anaerobic bacteria, low bactericidal activities were determined in both studies (mean peak titers ranged from 1:2.1 to 1:3.1; mean trough titers range from 1:2.0 to 1:2.9). In clinical settings with severe mixed infections, a parenteral therapy consisting of modern quinolones together with clindamycin or imidazole derivatives seems to be active and offers no obvious interactions.

4-Quinolones↗

PubMed1990

Pharmacokinetics of FCE 22891, a new oral penem.

FCE 22891 is the oral prodrug of FCE 22101, a new broad-spectrum penem. The pharmacokinetics of FCE 22891 after single-dose administration, its absolute bioavailability, and the effect of food intake on its absorption were investigated in three different randomized crossover studies in healthy volunteers. Drug levels in blood and urine were measured by high-pressure liquid chromatography and bioassay. For optimal comparison of the results of all studies, and since there was good agreement of both methods, only the high-pressure liquid chromatography results are included. The pharmacokinetics of the penem were linear, and its bioavailability after oral administration was 42 +/- 11%. Food intake increased the total area under the curve from 0 h to infinity from 11.9 +/- 3.5 to 14.1 +/- 2.4 mg.h/liter. A specific side effect, i.e., bladder complaints, was registered in some volunteers taking FCE 22891 at doses greater than or equal to 1.0 g.

Administration, Oral↗

PubMed1990

Comparative pharmacokinetics of glycopeptide antibiotics, and the influence of teicoplanin on granulocyte function.

The glycopeptide antibiotics teicoplanin and vancomycin differ in their pharmacokinetic properties. Teicoplanin is characterized by a high and prolonged serum concentration as a result of its long elimination half-life, which can be explained by high serum protein binding and renal tubular resorption. The apparent volume of distribution of teicoplanin is much larger than the extracellular space of the human body, indicating intracellular accumulation in different tissues. Elimination is primarily via the kidneys, though 15-20% is eliminated by non-renal mechanisms. Vancomycin has a shorter elimination half-life and lower protein binding than teicoplanin. At therapeutically relevant serum concentrations, teicoplanin has no influence on superoxide anion production and enzyme release by granulocytes.

Cells, Cultured↗

PubMed1989

Ciprofloxacin intravenous dose variance.

Following different intravenous dosages of ciprofloxacin in volunteers, only limited variation in serum concentrations have been reported using volunteers in both single- and multiple-dose studies. In patients, a greater variability in serum concentrations was reported during intravenous ciprofloxacin treatment. This was also the case in patients with varying degrees of renal insufficiency. However, no report exists of nonmeasurable ciprofloxacin serum concentrations during intravenous treatment in patients.

Adult↗

PubMed1989

Combination effects of ciprofloxacin, clindamycin, and metronidazole intravenously in volunteers.

Despite the broad antibacterial spectrum of ciprofloxacin, most anaerobic organisms are resistant to the drug, whereas several gram-positive organisms are only moderately susceptible. Thus, in some clinical situations, combined treatment with ciprofloxacin and metronidazole or clindamycin could be useful. Therefore, the pharmacokinetics and serum bactericidal activities of ciprofloxacin in combination with clindamycin or metronidazole were investigated using a randomized crossover study design in 10 healthy volunteers. Ciprofloxacin (200 mg) was administered alone and in combination with clindamycin (600 mg) or metronidazole (500 mg); all drugs were given intravenously over 30 minutes. Serum and urine concentrations of the substances were measured using standard methods (high-performance liquid chromatography or gas chromatography). Blood samples for determination of serum bactericidal activity against five different aerobic and two anaerobic bacterial species (a total of 58 strains) were obtained one hour and six hours after drug infusion. All values were statistically analyzed by use of the Student t test.

Adult↗

PubMed1989

Pharmacokinetics of ticarcillin/clavulanate in severely burned patients.

A pharmacokinetic trial with ticarcillin/clavulanate was undertaken in patients with severe burns. Timentin 5.2 g (ticarcillin 5 g + clavulanate 200 mg) was administered by iv infusion over 20 min, two or three times daily. Fifteen patients with varying amounts of total body surface (TBS) burned could be evaluated for pharmacokinetic calculations (group A, greater than 20% TBS, n = 7; group B, less than 10% TBS, n = 8). Both groups presented similar pharmacokinetic behaviour. Compared with healthy volunteers, the volume of distribution for both ticarcillin and clavulanate was increased 2.5 times. For ticarcillin the mean elimination half-lives in serum were 95.1 (A) and 86.1 min. (B), respectively; for clavulanate, the half-lives were 144.0 (A) and 132.1 min (B), respectively. The 0-8-h urine recovery of ticarcillin was 84% (A) and 83% (B), and for clavulanate it was 86% (A) and 88% (B) of the administered dose. As a consequence of the increased distribution volumes and the increased AUC's in severely burned patients the highest recommended dose of ticarcillin/clavulanate appears suitable.

Burns↗

PubMed1989

Penetration of amoxycillin/clavulanate into human bone.

Twenty patients undergoing orthopaedic surgery for total hip replacement received a single prophylactic intravenous dose of 2.2 g Augmentin (2 g amoxycillin + 200 mg clavulanate). Bone samples removed during the operation were saved for amoxycillin and clavulanate assay. The proportion of inorganic matter in the bone samples was determined to calculate the concentrations of the drugs in their distribution volume. The cortical and cancellous bone were penetrated to a comparable extent by both compounds yielding maximum concentrations at one hour after the end of the infusion. The mean concentrations of amoxycillin in the cortex and spongy layer were 26.0 and 18.2 mg/kg within 1 h, 23.8 and 19.8 mg/kg in the interval from 1 to 2 h after infusion, and 9.2 and 5.9 mg/kg between 2 and 5 h. The corresponding values for clavulanate were 2.3 and 1.6 mg/kg, 2.5 and 1.6 mg/kg, and 1.0 and 0.7 mg/kg, respectively. No postoperative wound infections occurred in these patients.

Aged↗

PubMed1989

Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid.

Two randomized double-blind crossover studies and one randomized crossover study were performed to document possible drug-drug interactions between antacids (aluminum magnesium hydroxide, 10 ml per dose for 10 doses), antimuscarinic drugs (pirenzepine, 50 mg per dose for 4 doses), and H2-blockers (ranitidine, 150 mg per dose for 3 doses) and amoxicillin (1,000 mg), cephalexin (1,000 mg), doxycycline (200 mg), and amoxicillin-clavulanic acid (625 mg). Ten healthy volunteers participated in each study. Concentrations in serum and urine were measured by bioassay, and pharmacokinetic parameters were calculated by the usual open one- or two-compartment models (statistics were determined by the Wilcoxon test). The antacid, pirenzepine, and ranitidine had no influence on the bioavailability of amoxicillin, cephalexin, and amoxicillin-clavulanic acid. Only small differences could be observed in the pharmacokinetic parameters, but they are not of therapeutic importance. However, the antacid caused a significant (P less than 0.01) reduction in the gastrointestinal absorption of doxycycline (area under the concentration-time curve, 38.6 +/- 22.7 mg.h/liter, fasting; 6.0 +/- 3.2 mg.h/liter, with antacid), resulting in subtherapeutic levels of doxycycline.

Adult↗

PubMed1989

Unique aspects of quinolone pharmacokinetics.

Despite some limited differences in pharmacokinetic parameters among the newer quinolones, their pharmacology is characterised by high volumes of distribution, long elimination half-lives, good to excellent bioavailability, low protein binding, limited biotransformation and different elimination pathways (mainly through the kidneys). The unique aspects of quinolones in comparison with beta-lactams and aminoglycosides are their higher volumes of distribution, longer elimination half-lives and their intracellular high concentration, especially in phagocytic cells.

4-Quinolones↗

PubMed1989

The pharmacokinetics of sultamicillin.

Sultamicillin is a mutual prodrug of ampicillin and sulbactam, a beta-lactamase inhibitor. When administered orally, sultamicillin is readily absorbed and rapidly hydrolyzed to provide high levels of its two constituents in the peripheral circulation. Peak serum concentrations of ampicillin are achieved that are approximately three and one-half times those obtained with an equivalent amount of oral ampicillin. Equimolar concentrations of sulbactam are also provided, with both ampicillin and sulbactam being widely distributed among various body fluids and tissues. The pharmacokinetic parameters of the two components are similar, both being eliminated primarily by renal excretion. Although the elimination half-lives of ampicillin and sulbactam are each approximately 1 hour, the high serum concentrations achieved coupled with their synergistic bactericidal activity permit twice-daily dosing.

Amoxicillin↗

PubMed1988

Comparative pharmacokinetics of intravenous ofloxacin and ciprofloxacin.

In ten volunteers the pharmacokinetics of ofloxacin and ciprofloxacin were determined after crossover administration of 100 and 200 mg intravenously (30 min constant infusion). Concentrations in serum and urine were measured by HPLC. Concentrations in serum following parenteral ofloxacin dosages demonstrated dose dependency with long biological half-lives. Pharmacokinetic parameters were calculated on the basis of an open three-compartment model, which resulted in a high volume of distribution for both substances (166-246 1 for ofloxacin, 178-2611 for ciprofloxacin). AUC for ofloxacin was three times higher than that for ciprofloxacin. Approximately 80% of ofloxacin and 57% of ciprofloxacin were eliminated through the kidneys. Ciprofloxacin had a considerable amount of extrarenal clearance, whereas only 19% of ofloxacin were eliminated by extrarenal mechanisms. Only 4.3% of ofloxacin after iv dosing could be detected as metabolites in urine.

Adult↗