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Biomedical subjects

T Bergan

Publications and source records attributed to T Bergan.

At least 73 records · Page 4Linked to original sources
PubMed1986

Pharmacokinetics of ciprofloxacin after intravenous and increasing oral doses.

The pharmacokinetics of ciprofloxacin were evaluated after increasing single oral doses of 100, 250, 500 and 1000 mg, and an intravenous dose of 100 mg given to each of 12 healthy volunteers (6 females and 6 males). Concentrations in serum and urine were determined by microbiological assay. The rise in peak serum concentrations and the values of the total area under the serum concentration curve were proportional to the increase in the oral doses. As the oral dose increased a slight increase was observed in the apparent time lag before absorption from 0.34 h after 100 mg to 0.53 h after 1000 mg. The serum half-life after the intravenous dose was 3.2 h. After the oral doses shorter apparent half-life values were observed. The intravenous dose showed an elimination phase distribution volume of 2.76 l/kg and total body clearance of 40.7 l/h. The total urinary excretion was 42.2 +/- 15.6% of the dose after the intravenous dose; the figure was lower after the oral doses. The bioavailability of the 100 mg oral dose was 83.7% as calculated from the value of the total area under the serum curve after the same oral and intravenous dose in all 12 subjects. Ciprofloxacin thus demonstrates normal linear pharmacokinetics, the rise in serum concentrations being proportional to the dose.

Administration, Oral↗
PubMed1986

Penetration to peripheral human lymph of clavulanic acid and ticarcillin.

An intravenous dose of 3.0 g ticarcillin and 0.2 g clavulanic acid was given to 11 healthy human volunteers in whom peripheral lymph, serum and urine were monitored for 8 h. The concentrations were assayed microbiologically. The mean levels in lymph collected during the period 0-1 h was 39.3 mg/l of ticarcillin and 2.93 mg/l of clavulanic acid. The mean peak concentration in lymph (appearing between 1.25 and 2.25 h) was 66.3 mg/l for ticarcillin and 4.1 mg/l for clavulanic acid. Elimination was slightly slower from lymph than from serum, the half-life being only 1.04 times longer from lymph than from serum for ticarcillin, but 1.22 times longer for clavulanic acid. The total areas under the concentration curves in lymph was 58% of the serum value of ticarcillin and 81.0% of clavulanic acid. This reflects the ability of the substances to penetrate to lymph. The mean 8-h urinary recovery was 63.7% of the dose of ticarcillin and 43.8% of clavulanic acid. The total body clearances were 14.61/h for ticarcillin and 7.91/h for clavulanic acid and the corresponding d beta distribution volumes 12.21 and 19.11. The ratio of the concentrations of ticarcillin to clavulanic acid in all body fluids increased with time. Pharmacokinetically, clavulanic acid is well suited to be given together with ticarcillin.

Adult↗
PubMed1986

Ofloxacin: serum and skin blister fluid pharmacokinetics in the fasting and non-fasting state.

Using an agar well diffusion assay, the concentrations of ofloxacin were measured in serum and skin blister fluid after an oral dose of 300 mg given with or without a standardized meal. The apparent lag time was longer when the drug was taken with food than in the fasting state and the serum peak concentrations occurred later; the rates of absorption being 1.72 +/- 1.12/h (S.D.) and 3.40 +/- 1.56/h respectively. The mean peak concentrations of each individual in serum and blister fluid were 3.8 +/- 1.6 mg/l and 1.7 +/- 0.5 mg/l, respectively, when the drug was taken with food, compared with 4.2 +/- 1.9 mg/l and 2.1 +/- 0.7 mg/l in the fasting state. The rate of penetration into blister fluid was not influenced by the intake of food. The elimination half-life was 9.0 +/- 6.2 h in serum and 13.5 +/- 7.8 h in blister fluid when the volunteers were fasting. The corresponding values in the non-fasting state were 6.3 +/- 5.5 h and 10.6 +/- 4.6 h. The ratio of the area under the concentration versus time curve (AUC0-infinity) for blister fluid and serum was 1.20 +/- 0.70 when ofloxacin was given without food and 1.03 +/- 0.34 when given with the meal.

Adult↗
PubMed1986

Pharmacokinetics of ciprofloxacin and effect of repeated dosage on salivary and fecal microflora.

The pharmacokinetics of ciprofloxacin was studied in 12 volunteers during a 5-day course of 500 mg of ciprofloxacin given orally twice a day. The effects on the microflora of saliva and feces were also examined. Serum and urine samples were assayed for ciprofloxacin microbiologically, and the salivary and fecal microflora were examined quantitatively after processing onto a series of selective media. Fecal samples were also investigated for the presence of Clostridium difficile and its cytotoxin. The MICs for new colonizing bacteria were examined in the salivary and fecal samples. There was no accumulation during the course of 5 days with peak serum concentrations identical (2.8 and 2.3 mg/liter) after the first and final doses, and the areas under the serum curves were similar (9.6 mg/liter). The serum half-life was 2.5 h on both days. The changes in the salivary flora were minor and affected only the neisseriae. In the fecal flora, the numbers of enterobacteria and enterococci decreased markedly, whereas the changes in anaerobic flora (anaerobic cocci, fusobacteria, and bacteroids) were not so pronounced. However, 14 days after the drug was discontinued, the salivary and fecal flora were normalized in all respects. No new colonization of ciprofloxacin-resistant bacteria for which MICs were above 1.0 mg/liter was observed. C. difficile or its cytotoxin was not detected.

Adult↗
PubMed1986

Extravascular penetration of highly protein-bound flucloxacillin.

The pharmacokinetics of intravenously administered flucloxacillin (2.0 g to five volunteers) are described. The passage of flucloxacillin to peripheral lymph and suction skin blisters was monitored. This drug was selected because the high serum protein binding of 96% offered a particularly good opportunity for the study of the impact on tissue penetration. Flucloxacillin was assayed by high-pressure liquid chromatography, and pharmacokinetics were assayed by computerized curve fitting to accepted models. Penetration of flucloxacillin to extravascular foci was rapid. After 30 min the drug concentrations were 0.5 +/- 0.3 microgram/ml in lymph and 0.9 +/- 0.7 microgram/ml in blister fluid. The peak concentration was 11.7 +/- 5.6 micrograms/ml in lymph and 4.6 +/- 1.4 micrograms/ml in blister fluid. Concentrations in urine were above 111 +/- 50 micrograms/ml throughout the 8-h monitoring period, and urinary recovery was 60.4%. The half-life was 2.1 +/- 0.9 h in serum, 1.4 +/- 0.6 h in lymph, and 11.0 +/- 4.1 h in blister fluid. The differences in half-life were significant (P less than 0.05) between serum and blister fluid but not between lymph and serum. Penetration, as represented by the mean ratios of areas under the curve, was 19.7 +/- 8.1% to lymph and 38.2 +/- 11.7% to blister fluid. The flucloxacillin distribution volume during the phase of elimination was 36.4 +/- 16.0 liters and the total body clearance was 12.9 +/- 5.5 liters. Flucloxacillin showed good tissue penetration, considering its very high serum protein binding. High flucloxacillin levels in lymph and blister fluid were explained in part by drug affinity to extravascular albumin. The major impacts of high protein binding are (i) slightly slower passage into extravascular sites, (ii) slightly later peak concentration, and (iii) levels in extravascular fluid that are persistently below those in serum.

Adult↗
PubMed1986

Pharmacokinetics of oral co-trimazine and the penetration of its components sulfadiazine and trimethoprim into peripheral human lymph.

Five healthy informed male volunteers received oral doses of 820 mg sulfadiazine (SDZ) plus 180 mg trimethoprim (TMP) (co-trimazine) every 24 h. Concentrations in serum, peripheral lymph from the leg and urine were determined after the first dose, and on the 4th day to reflect approximate steady-state conditions. TMP was assayed microbiologically and unchanged SDZ by high-pressure liquid chromatography. There was a rise in concentrations from the first dose to the 4th day. The rise for SDZ was by a factor of 1.6 in both serum and lymph; the rise for TMP was also 1.6 in serum, but 1.5 in lymph. The peak concentrations at steady state were 27.7 mg/l (SD) +/- 4.3 SDZ, and 1.6 +/- 0.68 mg/l TMP. The serum values at that time were 31.7 +/- 5.8 mg/l SDZ and 2.3 +/- 0.51 mg/l TMP. The simultaneous concentrations of both SDZ and TMP were always somewhat lower in lymph than in serum, also at the end of the observation periods, i.e. 12 h after the first dose and 72 h after the final one. But the serum concentrations of both SDZ and TMP were only slightly higher than in lymph. After the final dose, the ratio between the 12-hour areas under the concentration curves of lymph and serum was 0.68 +/- 0.12 for SDZ and 0.59 +/- 0.14 for TMP. The values after the first dose were similar, 0.63 +/- 0.17 and 0.57 +/- 0.05, respectively. The elimination half-life in serum during steady state was 16.5 h for SDZ, 8.6 h for acetylated SDZ and 9.4 h for TMP. In lymph the corresponding values were 19.2, 19.2 and 8.9 h.

Adult↗
PubMed1986

Pharmacokinetics of metronidazole and its metabolites in reduced renal function.

The pharmacokinetics of metronidazole (M), hydroxymetronidazole (OH-M), and acetylhydroxymetronidazole (A-M) were determined after a single intravenous dose of 0.5 g metronidazole. This was administered as an intravenous infusion during 30 min to 10 healthy volunteers and 24 patients with varying degrees of reduced renal function. Serum and urine concentrations were assayed by high-pressure liquid chromatography. The peak concentrations of the hydroxymetabolite appeared within an hour in the healthy volunteers and after a mean of 2.6 h (range 0.5-12.5 h) in the patients with reduced renal function. Analogously, the peak of the acetylmetabolite appeared later, at an average of 6.9 h and a range of 0.5-36.5 h. A-M was not observed in serum of the healthy subjects nor in 6 of the patients, but was recovered in urine of all subjects. The serum concentrations of M and OH-M were detectable throughout the 48 h monitored. Total urinary recovery in healthy subjects was 108.0% of the dose. This breaks down to 18.4% metronidazole, 62.4% OH-M, and 27.2% A-M. In the patients with reduced renal function, the relative contribution of A-M is higher than that of the other two products. The serum half-life of metronidazole was 7.1 in the healthy subjects and similar in reduced renal function (range 3.5-12.4 h). The serum half-life of OH-M was 18.0 h in the healthy and ranged 9.6-85.5 h in renal impairment. Long half-life values of 8.5-36.5 h were observed for A-M. Accumulation of OH-M and particularly of A-M was marked in reduced renal function. In the normal healthy volunteers, the coefficient of the steady-state distribution volume averaged 0.404 liter/kg of the terminal phase distribution volume 0.542 liter/kg, and the total body clearance 3.1 liter/h. The total body clearance of the unchanged compound was not influenced by reduced renal function.

Adult↗
PubMed1986

Human pharmacokinetics and skin blister levels of sulfonamides and dihydrofolate reductase inhibitors.

The penetration into suction skin blisters and pharmacokinetics of 4 sulfonamides (sulfacarbamide, sulfadimidine, sulfadiazine, sulfamethoxazole) and two dihydrofolate reductase inhibitors (methioprim, trimethoprim) have been compared in healthy volunteers. The concentrations were monitored after the first dose and for the subsequent 4 days when approximate steady state conditions could be assumed to have been established. The serum or plasma half-life of the agents in the above order was 3.1, 6.3, 13.9, 12.1, 9.3, and 12.0 h. The respective areas under the serum curves were 97.1, 607.8, 942.6, 1423.1, 128.1 and 175.4 mg/l per dose of 1.0 g. With the sulfonamides, there was a distinct correlation between serum protein binding and pKa and the ability of the compounds to penetrate into blister fluid as shown by the 12-hour ratios between areas under the concentration curves in blister fluid relative to serum.

Adult↗
PubMed1986

Crystalluria and ciprofloxacin, influence of urinary pH and hydration.

Ciprofloxacin is one of the newer 4-quinolones. It combines a high antibacterial activity and a broad spectrum with favourable pharmacokinetic properties. The present study was designed to detect the influence of urinary pH and fluid consumption on crystalluria. Six healthy volunteers aged 25-41 years, 3 of each sex, participated in the study. Single doses of 1,000 and 500 mg of ciprofloxacin were given orally. The urinary pH was varied by giving each subject three different diets: a regular diet, a diet supplemented by ammonium chloride to acidify urine, and a diet supplemented by sodium bicarbonate to obtain alkaline urine. The urine volume and pH were measured and microscopically examined at 37 degrees C immediately after voiding. After the very high dose of 1,000 mg ciprofloxacin the regular diet regimen led to crystalluria in only one subject. Even with this high dose, but with the acidifying regimen, no crystals were observed in any one of the volunteers. When bicarbonate was supplemented 5 to 6 volunteers presented crystals in 22 of the 36 urine samples. 21 of the crystalluric urine samples showed a pH greater than or equal to 7.3. After the usual 500-mg dose and regular diet no crystals were observed at all; only in 3 subjects who received bicarbonate supplement crystals have been seen. In the urine of two subjects crystals emerged 'ex vivo' after some hours of storage at both 37 degrees C and room temperature; these results show the importance of sediment observation at 37 degrees C immediately after voiding to differentiate between real and 'ex vivo' crystalluria. Results of different examinations permit the conclusion that the crystals contain mostly unchanged ciprofloxacin as major component and magnesium as characteristic element. Participation of the metabolite 2 in the crystal formation cannot be excluded. No significant change was observed in blood counts and blood chemistry of any subject. Urinalysis showed no modifications except the eventual presence of the typical drug-related crystals. Hematuria never occurred.

Adult↗
PubMed1986

Pharmacokinetics of co-trimazine (sulphadiazine plus trimethoprim) in geriatric patients.

The study was aimed at analyzing the pharmacokinetics of sulphadiazine (SDZ) and trimethoprim (TMP) in geriatric patients and was carried out in two stages. The first stage compared 11 geriatric patients (68-89 years old) and 9 healthy volunteers (21-34 years old). Serum concentration and urine elimination were determined on day 4 after 12-hourly administration of 1 tablet of co-trimazine containing 410 mg sulphadiazine (SDZ) plus 90 mg trimethoprim (TMP). The mean serum concentrations of SDZ were significantly higher in the older subjects than in the volunteers after 1, 8 and 12 h (p less than 0.05, 0.01, 0.01), but were not differentiable after 2 or 4 h. For TMP, the serum levels were higher (p less than 0.05) in the patients only after 8 h. The amounts collected in urine were higher in the normal volunteers for SDZ during the intervals 0-2 h (p less than 0.05), 2-4 h (p less than 0.01), and 4-8 h (p less than 0.01), but not for 8-12 h. The 12-hour recovery was 69% SDZ + acetyl-SDZ recovered in the patients compared to 66.0% in the volunteers. Indistinguishable amounts of TMP were recovered during each interval in the two groups of subjects, 59.2% in the patients compared to 70.0% in the volunteers. The second stage of the study comprised 9 geriatric patients of mean age 83.6 years and creatinine clearance 59.2 ml/min who were followed for 11 days. A steady increase in serum levels was observed. The mean peak serum concentration for SDZ was 16.7 +/- 4.2 mg/l after the first dose and 44.7 +/- 11.3 mg/l on day 10. For acetyl-SDZ, the respective concentrations were 2.1 +/- 0.9 and 7.1 +/- 3.1 mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Impact of azlocillin on the colon microflora.

To evaluate the impact of parenteral azlocillin therapy on human colon microflora, faecal specimens were taken from 6 patients before, during and after therapy for analysis of the microflora. In 2 patients major changes took place. Thus the numbers of streptococci, Escherichia coli, anaerobic cocci, lactobacilli, clostridia and bacteroides decreased markedly during therapy. One of these patients was colonized with azlocillin-resistant Enterobacter cloacae. The other 4 patients had only minor changes in the microflora. Variations between patients seem to exist. Pronounced alterations in the colonic flora may have clinical implications.

Adult↗
PubMed1986

Pharmacokinetic differentiation and consequences for normal microflora.

The pharmacokinetic properties of a drug are decisive for effective antibacterial therapy, the ability of the drug to reach a site of infection, but they also contribute to whether concentrations become undesirably high in places where the antibiotics are not wanted but where they may interfere with the normal microflora. The microflora in the intestines is particularly important because of the sheer numbers of bacteria present there and the consequences of imbalance such as diarrhoea and selection of bacteria resistant against antibiotics. For these reasons, high intestinal absorption, as can be achieved by the ampicillin prodrugs, is important. This leads to high utilization of the dose and decisively reduces the frequency of loose stools and diarrhoea. Improvement of biopharmaceutical properties of oral dosage forms need combined pharmaceutical and pharmacokinetic assessment. High elimination in the bile can have a considerable impact on the intestinal microflora as, for instance, agents with broad spectrum, like beta-lactamase stable cephalosporins that are not absorbed but remain within the gastrointestinal tract. Cephalosporins have been implicated in the selection of beta-lactamase producing enterobacteria. Narrow spectrum has been a sales argument, but if these agents produce high intestinal concentrations, as is the case with formulations of erythromycin that have poor formulations and are incompletely absorbed, the result may be disturbed faecal flora. In addition to low absorption, erythromycin elimination by bile is high. Clostridium difficile may in particular be selected by high concentrations of antibacterial drugs in the intestines.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1986

Pharmacokinetic evaluation of cefsulodin in children with and without cystic fibrosis treated for infectious diseases.

The pharmacokinetic characteristics of cefsulodin have been studied in 7 patients suffering from cystic fibrosis (CF) and compared to the findings in 6 children without CF. They were given intravenous bolus doses (3 min) of 40 mg/kg. The antibiotic concentrations were assayed by high-pressure liquid chromatography. The serum concentrations were lower in the CF group as reflected by the mean total area under the serum concentration curves of 180 vs. 309 mg h/1, and the serum concentrations after 8 hours which were below the detection limit in the CF patients compared to 4.7 mg/l in the non-CF. The patients with cystic fibrosis had a not significantly lower total body clearance (5.8 vs. 7.0 1/h). The serum half-life was slightly shorter in patients with CF (1.2 vs. 1.4 hours). Consequently, given microbes of the same MIC's, patients with CF should receive higher doses than those recommended for patients without cystic fibrosis.

Adolescent↗
PubMed1986

Pharmacokinetics of azlocillin in children with and without cystic fibrosis treated for infectious diseases.

The pharmacokinetic characteristics of azlocillin were compared in 7 children with cystic fibrosis (CF) and 6 children without this disease who were all treated for infectious diseases. Azlocillin was administered as intravenous bolus injections in doses of 200 mg/kg. The serum concentrations were somewhat lower in CF than in non-CF as reflected by total areas under the serum concentration curves of 594 and 677 mg h/1, and serum levels after 8 hrs of 10.7 mg/1 in non-CF vs. a concentration below the detection limit in CF. The CF children had a lower serum half-life (1.1 hrs) than the children without this disease (3.3 hrs). The difference is explained by higher total body clearance in CF (12.7 1/h) than the non-CF group (8.4 1/h). The dose interval should either be shorter, or the doses increased, when azlocillin is administered to patients with CF.

Adolescent↗