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Biomedical subjects

T B Vree

Publications and source records attributed to T B Vree.

At least 199 records · Page 11Linked to original sources
PubMed1986

Toxicologic and pharmacokinetic evaluation of a case of vancomycin intoxication during continuous ambulatory peritoneal dialysis.

The use of vancomycin is rapidly increasing due to the emergence of strains of staphylococci resistant to betalactam antibiotics. In this communication the pharmacokinetics of an overdose of vancomycin in a patient during continuous ambulatory peritoneal dialysis (CAPD) is reported. Brainstem auditory evoked potentials (BAEPs) are used to assess ototoxicity. It could be shown that by shortening the dwell time, the apparent CAPD flow was increased and the vancomycin clearance was also increased. This may explain in part the differences in the values of vancomycin t1/2 in this patient (21 h) as compared to other studies (60-120 h). The age of the patient (3.5 years) may also have influenced the t1/2. Using brainstem auditory evoked potentials as a parameter to assess ototoxicity, it was shown that this patient suffered no damage from the overdose.

Creatinine↗
PubMed1986

Pharmacokinetics: metabolism and renal excretion of quinolones in man.

The quinolones are relatively poorly absorbed from the gastrointestinal tract. The elimination proceeds mainly by renal excretion. The half-life of elimination depends on the molecular structure and varies between 2 and 10 h. Impaired kidney function is expected to increase the half-life of elimination, though this effect is not always observed. Since the 4-oxo-metabolites show a higher renal clearance than the parent drug, renal impairment will result in a cumulation of the metabolites in the body.

Anti-Infective Agents↗
PubMed1986

Pharmacokinetics of intravenously administered ciprofloxacin in intensive care patients with acute renal failure.

The pharmacokinetics of ciprofloxacin after a single intravenous administration of 100 mg were studied in intensive care patients with an acute renal impairment. There was no correlation found between the creatinine clearance and the renal clearance of ciprofloxacin. This applies to the entire group of patients. The decrease in renal clearance of ciprofloxacin was, however, more pronounced than the change in the elimination half-life, suggesting an important extra-renal elimination of the drug.

Acute Kidney Injury↗
PubMed1986

The effect of the 4-quinolone enoxacin on plasma theophylline concentrations.

In patients treated concomitantly with theophylline and enoxacin, a broad spectrum antibacterial agent for oral administration, unexpectedly high plasma theophylline concentrations were observed. In six patients receiving intravenous aminophylline under controlled conditions, enoxacin was started in a daily dose of 800 or 1200 mg. Plasma theophylline concentrations increased from 8.4 +/- 2.4 mg/l to 15.0 +/- 5.1 mg/l at day 3 of co-administration. Total body clearance of theophylline decreased significantly, whereas renal clearance and protein binding did not change. When enoxacin, 800 mg daily, was administered to seven patients with a stable chronic obstructive pulmonary disease, who were on long-term theophylline treatment a significant increase in plasma theophylline concentrations occurred as well: elimination half-life was prolonged. It is concluded that the rise of plasma theophylline concentrations is caused by a reduced metabolic clearance of theophylline. If concomitant use of both drugs is necessary, monitoring of plasma theophylline concentration and adjustment of the theophylline dose is recommended, to avoid toxicity.

Adult↗
PubMed1986

Dosage adjustment for ceftazidime in patients with impaired renal function.

Ceftazidime has good antibacterial activity against many Gram-negative micro-organisms including Ps. aeruginosa. The aim of the present study was to calculate a dosage adjustment regimen for renal failure patients and to test it in a second group of patients. A study was made of the pharmacokinetics of ceftazidime 1 g given as a single bolus i.v. injection in 20 patients in an intensive care unit with varying degrees of renal function, including patients on regular haemodialysis. The serum half-life of elimination (t1/2 beta) varied from 1.6 to 45 h depending on renal function. During haemodialysis the mean t1/2 was 4.7 h. A good correlation between the renal clearance of creatinine and ceftazidime was observed. In most patients protein binding was lower than previously observed. From the pharmacokinetic data, a dosage adjustment regimen for patients with renal insufficiency was calculated, which studies in 7 further patients showed to be effective.

Adult↗
PubMed1986

Renal excretion and pharmacokinetics of methotrexate and 7-hydroxy-methotrexate following a 24-h high dose infusion of methotrexate in children.

In children with lymphoid malignancies 18 courses of methotrexate (18-200 mg/kg) administered as a 24-h infusion were monitored. Plasma concentrations and renal excretion rates of methotrexate (MTX) and 7-hydroxymethotrexate (7-OHMTX) were determined. A low correlation was found between the administered dose of MTX and the body exposure to MTX or 7-OHMTX. Although 84% of the MTX eventually recovered from the urine was excreted during the 24 h of the infusion, the renal clearance of MTX was markedly lower during the time of the infusion than after it. There were courses with a low and others with a high renal clearance of MTX during the infusion, despite the same urine flow. A low MTX renal clearance was correlated with a high body exposure to MTX. As the same variations were also seen in the same patient during successive courses, pharmacokinetical characterization of patients appears questionable. The renal clearance of 7-OHMTX was significantly lower than the renal clearance of MTX, and the body exposure to 7-OHMTX ranged from 2-40% of the MTX body exposure. Treatment courses with a low or a high body exposure to 7-OHMTX were not associated with different urinary recoveries of the metabolite. Differences in MTX hydroxylation could not be substantiated. Because the concentration of 7-OHMTX is high soon after the end of an infusion, a specific method of MTX determination should be chosen for controlling treatment.

Child↗
PubMed1986

Pharmacokinetics, renal clearance, tissue distribution, and residue aspects of sulphadimidine and its N4-acetyl metabolite in pigs.

Pharmacokinetics and tissue distribution experiments were conducted in pigs to which sulphadimidine (SDM) was administered intravenously, orally, and intramuscularly at a dosage of 20 mg SDM/kg. SDM was acetylated extensively, but neither hydroxy metabolites nor their derivatives could be detected in plasma, edible tissues or urine. Following i.v. and two oral routes of administration, the N4-acetylsulphadimidine (N4-SDM) concentration-time curve runs parallel to that of SDM. The percentage of N4-SDM in plasma was in the range between 7 and 13.5% of the total sulphonamide concentration. The bioavailability of SDM administered in a drench was 88.9 +/- 5.4% and administered mixed with pelleted feed for 3 consecutive days it was 48.0 +/- 11.5%. The renal clearance of unbound SDM, which was urine flow related, was 1/7 of that of creatinine, indicating reabsorption of the parent drug. The unbound N4-SDM was eliminated three times faster than creatinine, indicating that tubular secretion was the predominant mechanism of excretion. After i.v. administration, 51.9% of the administered dose was recovered in urine within 72 h p.i., one quarter of which as SDM and three quarters as N4-SDM. Tissue distribution data obtained at 26, 74, 168, and 218 h after i.m. injection revealed that the highest SDM concentration was found in plasma. The SDM concentration in muscle, liver, and kidney ranged from one third to one fifth of that in plasma. The N4-SDM formed a minor part of the sulphonamide content in edible tissues, in which the SDM as well as the N4-SDM concentration parallelled the plasma concentrations. Negative results obtained with a semi-quantitative bioassay method, based on monitoring of urine or plasma, revealed that the SDM concentration levels in edible tissues were in that case below 0.1 mu/g tissue.

Administration, Oral↗
PubMed1986

Pharmacokinetic, residue and irritation aspects of chloramphenicol sodium succinate and a chloramphenicol base formulation following intramuscular administration to ruminants.

The disposition of chloramphenicol (CAP) and of its glucuronide metabolite in plasma and milk was studied following a single intramuscular injection of a chloramphenicol base formulation (Amicol Forte; product A) and of chloramphenicol sodium succinate (product B) to dairy cows. The dose applied of both formulations was equivalent to 50 mg CAP base/kg body weight. The HPLC determined CAP concentrations were microbiologically active. Product A revealed 30% higher plasma CAP peak concentrations (13.0 vs 9.0 micrograms/ml) and 36% larger areas under the plasma concentration-time curves than product B, whereas their absorption and elimination half-lives were of the same order of magnitude. In the onset phase (during 4 h p.i.) unhydrolysed CAP sodium succinate could be detected in plasma and the glucuronide fraction was 26% of the parent drug. After 25 h p.i. the glucuronide fraction equalled that of the parent drug. The maximum CAP concentration in milk was for product B equal to, and for product A 80% of, the CAP plasma concentration. In milk no chloramphenicol glucuronide metabolites could be detected. HPLC methods for detecting ultra-trace CAP concentrations in edible tissues were developed by the employment of extraction with or without a clean-up procedure. Seven days after i.m. administration of product A and B to calves, the CAP residue concentrations in the kidney, liver, and muscle were less than 2 nanogram/g tissue. Traces of CAP residues could be still found at the injection site and in the urine. Chloramphenicol sodium succinate (product B) caused extensive tissue irritation at the injection site, while in the case of product A the irritation was limited.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Pharmacokinetics and renal clearance of oxytetracycline in piglets following intravenous and oral administration.

The pharmacokinetics of oxytetracycline (OTC) in three weaned piglets was studied following three routes of administration: intravenously, orally as drench, both at a dose of 20 mg/kg, and orally as medicated (400 ppm OTC) pelleted feed administered during 3 consecutive days. Analysis of the intravenous data according to the three compartment pharmacokinetic model revealed that OTC was well distributed in the body (Vf: 1.62 l/kg), had an overall body clearance of 0.25 litre/kg/h, and the elimination half-lives were in the range between 11.6 and 17.2 hrs. The mean OTC binding to plasma proteins was 75.5 +/- 4%. Following the drench route of administration the maximum plasma OTC concentration was achieved between 1 and 5 h post application and ranged between 1.18 and 1.41 micrograms/ml. The mean maximum plasma OTC concentration during medicated feed administration was 0.20 +/- 0.06 microgram/ml, which was achieved approximately 30 hours after the onset of the administration. A steady state OTC plasma level (approximately 0.2 microgram/ml) was maintained till the end of the trial. Within 48 hours after cessation of medicated feed administration the plasma OTC levels were beneath 0.06 microgram/ml. The mean OTC bioavailabilities of the oral routes were low: after the drench route of administration 9.0 +/- 0.67%, and after medicated pelleted feed administration 3.69 +/- 0.8%. The mean OTC renal clearances of each piglet ranged between 10.1 and 13.9 ml/min/kg (based on free OTC plasma fractions). The renal OTC clearance values were urine flow dependent in all piglets and significantly correlated with the renal creatinine clearance (P less than 0.005), being 3-5 times higher than the latter. It is concluded that in piglets OTC is excreted mainly by glomerular filtration and partly by tubular secretion. The potential clinical efficacy of 400 ppm OTC as medicated feed with respect to treatment, e.g. atrophic rhinitis, is discussed.

Administration, Oral↗
PubMed1986

Comparative pharmacokinetics, bioavailability and renal clearance of five parenteral oxytetracycline-20% formulations in dairy cows.

Oxytetracycline (OTC) concentrations on plasma and milk of dairy cows were determined following a single intramuscular injection of five oxytetracycline-20% formulations at a dosage of approximately 10 mg/kg. For obtaining pharmacokinetic reference parameters, one 10% OTC formulation was administered intravenously. The five 20% formulations were compared and evaluated pharmacokinetically with respect to absorption rate, peak plasma and milk OTC concentrations, biological half-life, and relative bioavailability. The mean maximum plasma OTC concentrations varied between 4.5 and 6.8 micrograms/ml and were achieved between 5 and 10 h p.i., depending on the formulation involved. The mean maximum milk concentrations, ranging from 1.12 to 1.92 micrograms/ml, were achieved 12 to 24 h p.i. A plasma OTC concentration exceeding 0.5 microgram/ml was maintained for 48 h to 70 h, and in milk for 33 to 49 h, depending on the formulation involved. Formulations exhibiting the lowest clinically noticeable irritation showed the highest peak plasma OTC concentrations and the best bioavailability. Among the formulations the calculated withholding periods for milk were in the range of 3 to 4 days and for edible tissues of 9 to 14 days. The OTC and creatinine clearances were significantly correlated to each other and to the urinary flow. OTC was excreted predominantly by glomerular filtration, partly by tubular secretion minus urogenital (distal renal tubuli and bladder) reabsorption.

Animals↗
PubMed1986

Enoxacin in lower respiratory tract infections.

In this open, non-comparative study 45 lower respiratory tract infections were treated with the new 4-quinolone, enoxacin. Special attention was paid to infections caused by Pseudomonas aeruginosa. Pseudomonas infections were treated with 600 mg bd. whereas infections caused by other bacteria were treated with 400 mg enoxacin bd. In 43 cases efficacy could be assessed. In six out of 23 cases Pseudomonas spp. were eradicated from the sputum. In 12 of the remaining 17 cases a clear reduction in bacterial numbers and a decrease of sputum volume and purulence were obtained. Clinical improvement or cure was obtained in 20 out of the 23 cases. Most of the causative microorganisms in the other infections were eradicated. In two patients Staphylococcus aureus persisted. Overgrowth with streptococci occurred in three patients. Adverse reactions were frequent and occurred in 29 out of 45 treatment periods. They were mainly related to the gastrointestinal tract and the central nervous system. In 25 out of 30 patients on concomitant treatment with theophylline an elevation of plasma theophylline concentrations occurred. Twelve of these patients developed signs and symptoms possibly related to theophylline toxicity. After treatment with enoxacin the MICs of most persisting Pseudomonas strains were two to four times higher than pre-treatment values.

Adult↗
PubMed1986

Clinical pharmacokinetics of carbamazepine and its epoxy and hydroxy metabolites in humans after an overdose.

In five cases of carbamazepine (CBZ) intoxication, the time curves of the plasma concentration and of the renal excretion rate of carbamazepine and its metabolites carbamazepine 10,11-epoxide (CBZ-epoxide) and trans-10,11-dihydro-10,11-dihydroxy-CBZ (CBZ-diol) were measured. Pseudo-steady-state or plateau-like plasma concentration-time curves were observed when doses of 12 or 18 g of CBZ were ingested. Hemoperfusion lowers the plasma concentration of CBZ and its metabolites by affecting the half-life. The effect of hemoperfusion is reduced by the continuous absorption from the gastrointestinal tract and redistribution from the tissues. The renal clearances of CBZ and of CBZ-epoxide are low (1 and 8 ml/min, respectively); both are flow dependent. The renal clearance of CBZ-diol is approximately 160-350 ml/min and is independent of the urine flow. Although urine stimulation increases the renal clearance of CBZ by 100%, the overall amount excreted increases only 1-2% of the dose. Protein binding of CBZ is approximately 80%, of CBZ-epoxide 50%, and of CBZ-diol 70%.

Adult↗
PubMed1986

Pharmacokinetics, metabolism, and renal excretion of sulfadimidine and its N4-acetyl and hydroxy metabolites in humans.

Sulfadimidine is acetylated and hydroxylated in humans. The hydroxylation pathways account for 10-20% of the dose, leaving the acetylation as the major metabolic pathway. The hydroxylation pathways are independent of the acetylator phenotype. The plasma concentration-time curve of sulfadimidine in fast acetylators is biphasic, with half-lives of 1.7 and 5.4 h, whereas that in slow acetylators is monophasic, with a half-life of 7.6 h. Hydroxylation of a methyl group in sulfadimidine lowers the protein binding from 90 to 60%, while acetylation does not affect the protein binding. Methyl hydroxylation markedly increases the renal clearance.

Acetylation↗
PubMed1986

The influence of quinolone derivatives on theophylline clearance.

Enoxacin decreases the metabolic clearance of the bronchodilator theophylline not only in severely ill patients, but also in patients with stable chronic obstructive airways disease. In this comparative study, significantly increased plasma theophylline concentrations were measured during co-administration of enoxacin (110.9%) and, to a lesser degree, also during co-administration of pefloxacin (19.6%) and ciprofloxacin (22.8%). Total body clearance of theophylline was significantly decreased by enoxacin (63.6%), ciprofloxacin (30.4%) and pefloxacin (29.4%). The pharmacokinetic parameters of theophylline did not change during co-administration of ofloxacin and nalidixic acid. There is growing evidence that the observed interaction is caused not by the parent drugs, but by the 4-oxo metabolite of enoxacin, pefloxacin and ciprofloxacin.

Aged↗
PubMed1986

Benzodiazepines and neuromuscular blocking drugs in patients.

The interaction between four benzodiazepines (diazepam, lorazepam, lormetazepam and midazolam) and two nondepolarizing neuromuscular blocking drugs (vecuronium and atracurium) was investigated in 113 patients during general anaesthesia. Neuromuscular function was monitored by recording the mechanical twitch tension of the adductor pollicis muscle of the thumb in response to ulnar nerve stimulation with single supramaximal stimuli of 0.2 ms at 0.1 Hz. In the first group of patients a benzodiazepine (diazepam 20 mg, lorazepam 5 mg, lormetazepam 2 mg or midazolam 15 mg), was injected i.v. 15 min before a single bolus of vecuronium 45 micrograms kg-1. In the second group of patients suxamethonium 1 mg kg-1 was given for endotracheal intubation, and 30 min later the patients received atracurium 200 micrograms kg-1. Fifteen min before injection of atracurium one of the same benzodiazepines as in the first group was injected i.v. Comparisons were made with control patients receiving thiopentone. Neither benzodiazepine caused significant potentiation of neuromuscular blocking agents in comparison with control. With midazolam, however, the duration to 25% and to 75% recovery of the twitch height after vecuronium was significantly longer than with diazepam. The time to 25% recovery of the twitch height after atracurium was significantly longer in patients receiving midazolam than in those receiving diazepam. The recovery index was not influenced by the four benzodiazepines.

Anesthesia↗