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Biomedical subjects

J Boelaert

Publications and source records attributed to J Boelaert.

At least 37 records · Page 2Linked to original sources

The pharmacokinetics of ciprofloxacin in patients with impaired renal function.

Pharmacokinetics of ciprofloxacin after single oral administration of 250 mg were studied in patients with and without renal failure. Ciprofloxacin concentrations were measured by HPLC. The elimination half-life was 8.7 +/- 0.9 h (mean +/- S.E.M.) in six renal failure patients not on haemodialysis, as compared to 4.4 +/- 0.2 h in six patients with normal renal function. The urinary recovery of unchanged ciprofloxacin was 5.3 +/- 1.7% of dose over 24 h in the renal failure patients, as compared to 37.0 +/- 3.7% in the patients with normal renal function. In haemodialysis patients, the half-life was 5.8 +/- 0.9 h on an interdialysis day, and 3.2 +/- 0.4 h during haemodialysis.

Administration, Oral↗

In vitro activity of temocillin against clinical isolates.

The minimum inhibitory concentrations of temocillin against more than 1000 clinical isolates were determined by an agar dilution method. Temocillin showed excellent activity against Haemophilus influenzae, pathogenic Neisseria species and Branhamella catarrhalis, including beta-lactamase producing strains, but showed very low activity or was inactive against Gram-positive cocci and Campylobacter, Bacteroides, Acinetobacter and Pseudomonas species. Good activity was obtained against 702 Enterobacteriaceae, including isolates resistant to the other penicillins and first- and second-generation cephalosporins, with 92% of all the strains inhibited at a concentration of 8 mg/L. However, the most striking property of temocillin was its high beta-lactamase stability which resulted in both a very narrow range of MICs within which all the isolates were inhibited, and a small influence of inoculum size on the MICs.

Bacteria↗

Effect of renal function and dialysis on temocillin pharmacokinetics.

Temocillin pharmacokinetics in renal impairment were investigated following an intravenous bolus injection of 15 mg/kg. The 28 patients were divided into 5 groups of varying renal function, from normal to uraemic [including a group being treated with haemodialysis and a group on continuous ambulatory peritoneal dialysis (CAPD)]. The distribution of temocillin into the tissues was not affected by renal dysfunction. Uraemia as compared to normal renal function resulted in a 4.3-fold decrease in temocillin clearance and a 3.1-fold decrease in urinary recovery over 24 hours, as well as a 5- and 3.7-fold increase in the beta half-life and the area under the curve (AUC), respectively. Haemodialysis doubled the serum clearance and halved the beta half-life of temocillin in the uraemic subject, but CAPD over 24 hours eliminated only 8% of the temocillin dose, resulting in a minimal change in pharmacokinetics. Temocillin dosage adjustments in renal failure are proposed.

Humans↗

Temocillin in the treatment of gram-negative septicaemia.

The effectiveness of temocillin in the treatment of culture-proven Gram-negative septicaemia was investigated in 22 adult patients, most of whom were elderly with serious underlying diseases. Administration of temocillin 2g twice daily to 15 patients or 1g twice daily to 7 patients resulted in clinical cure in 15 patients (68%), while 4 responded partially (18%) and 3 were considered failures (14%). The original pathogen was eradicated from 20 of 21 assessable patients (95%), 1 patient was unassessable and 1 was considered a failure. Superinfection was documented in 4 patients, originating twice in a central venous catheter, once in the urinary tract and once in an unidentified source. No clinical nor biological side effects were observed except for pain at the injection site in 1 patient who received the drug intramuscularly. We conclude that temocillin in monotherapy can be used effectively for proven Gram-negative septicaemia, and that the safety of the drug makes it particularly valuable in the elderly.

Aged↗

Plasma concentrations of nifedipine in patients with renal failure.

Plasma concentrations of nifedipine were measured after oral administration of a capsule (Adalat) containing 10 mg of the substance in 6 patients with renal failure not on haemodialysis, in 5 patients with renal failure on haemodialysis and in 6 patients with normal renal function. Whereas the presence of renal failure did not influence the plasma concentrations, lower concentrations were found in the patients on haemodialysis than in the other groups.

Administration, Oral↗

The pharmacokinetics of temocillin in patients with normal and impaired renal function.

The pharmacokinetics of temocillin was studied in 16 subjects with varying degrees of renal functional impairment. The subjects were divided into three groups, depending on their creatinine clearance: Group A greater than 70 ml/min/1.73 m2; Group B 20-70ml/min/1.73 m2 and Group C less than 20 ml/min/1.72 m2. Following intravenous administration the total serum clearance of temocillin was reduced in patients with renal insufficiency. The distribution of temocillin into the tissues was not affected by renal dysfunction, apparent distribution volumes being 15.11, 16.01 and 13.81 in Groups A, B and C respectively. The change in clearance was reflected in an increased area under the serum concentration versus time curve from 418 mg h/l in Group A to 1301 mg h/l and 1553 mg h/l in Groups B and C respectively. The beta elimination half-life was also prolonged from 3.5 h in Group A 12.7 h in Group B and 17.5 h in Group C. The urinary excretion of temocillin was both delayed and reduced according to the extent of kidney damage. The reduction in temocillin clearance was proportional to the extent of reduction from normal of the clearance of creatinine. This relationship has been used to suggest dosage schedules for temocillin in patients with renal insufficiency.

Adolescent↗

Decrease in renal function due to sulphinpyrazone treatment early after myocardial infarction.

Twenty-nine patients with recent myocardial infarction were randomly allocated to a placebo group (n = 14) and to a group (n = 15) who received sulphinpyrazone, 4 x 200 mg daily for 7 days. Renal function significantly and transiently deteriorated in the sulphinpyrazone group compared to the placebo group. In the sulphinpyrazone group the 24 hour-urinary prostaglandin E2 and kallikrein excretion were suppressed. These data suggest that the decrease in renal function caused by sulphinpyrazone early after myocardial infarction could be mediated by an inhibition of renal prostaglandin and/or kallikrein-kinin synthesis.

Acute Kidney Injury↗

Etiology of hypercalcemia in a patient with Addison's disease.

A case is reported of a hypercalcemic patient with primary Addison's disease. A combination of increased calcium input into the extracellular space and reduced calcium removal by the kidney accounted for the hypercalcemia. The mechanisms responsible for the reduction in calcium removal were decreased glomerular filtration and increased tubular calcium reabsorption. Both renal factors were secondary to volume depletion and improved rapidly during rehydration with saline infusion. The enhanced calcium mobilization was probably of skeletal origin. It persisted irrespective of volume status until hydrocortisone treatment was instituted. Serum 1,25-dihydroxyvitamin D3 levels were below 10 pg/ml, even after normalization of the glomerular filtration rate, but returned slowly to the normal range during corticosteroid substitution. Serum 25-hydroxyvitamin D3 and parathyroid hormone levels were within the normal range. Our case report therefore demonstrates that physiological amounts of glucocorticoids reduce bone resorption, normalize serum calcium, and restore the production of 1,25-dihydroxyvitamin D3.

Addison Disease↗

In vitro activity of temocillin (BRL 17421), a novel beta-lactam antibiotic.

The minimal inhibitory concentration of temocillin (BRL 17421) against 476 clinical isolates was determined by an agar dilution method. Temocillin was active against most of the Enterobacteriaceae, Haemophilus, and Neisseria strains tested. The compound showed low activity or was inactive against Bacteroides, Campylobacter, Acinetobacter, Pseudomonas, and Staphylococcus aureus strains. Within each species, individual strains showed a high degree of uniformity in their susceptibility to temocillin; the drug concentrations that inhibited the growth of 90% of organisms were the same or close to those which inhibited the growth of 50% of organisms. In contrast, the same strains showed a very wide range of susceptibility to the other antibiotics tested, including third-generation cephalosporins. Against strains of Enterobacteriaceae highly susceptible to third-generation cephalosporins, temocillin was considerably less active than cefotaxime, ceftazidime, and moxalactam, although it was more active than cefazolin and piperacillin. Against certain strains of Enterobacter and Citrobacter resistant to third-generation cephalosporins, temocillin was more active than cefotaxime and ceftazidime. An increase in the inoculum size did not alter the activity of temocillin, indicating that the compound has high stability to beta-lactamases. The minimal lethal concentration was also very similar to the minimal inhibitory concentration when an inoculum of 10(5) colony-forming units was used.

Bacteria↗