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Biomedical subjects

I Nilsson-Ehle

Publications and source records attributed to I Nilsson-Ehle.

At least 37 records · Page 2Linked to original sources
PubMed1992

Ciprofloxacin and the inner ear--a morphological and round window membrane permeability study.

This study was conducted in order to evaluate ototoxic potential and passage through the round window membrane of ciprofloxacin, a newly developed antimicrobial drug with an antibacterial spectrum well suited for the treatment of suppurative otitis media. Ciprofloxacin was injected intraperitoneally in 40 guinea pigs in doses ranging from 25 to 150 mg/kg body weight for 14 consecutive days. Sixteen inner ears of chinchillas were exposed to ciprofloxacin at a concentration of 0.1 mg/ml applied directly to the intact round window membrane. Despite severe deterioration of the animals injected with the highest doses, no behavioral or definite morphological evidence of inner ear or vestibular damage could be seen. Ciprofloxacin concentrations in the perilymph were determined with high-performance liquid chromatography. Direct passage of ciprofloxacin, presumably via the round window membrane, was demonstrated. After 1 h and 15 min, an arithmetic mean concentration of 0.165 micrograms/ml (95% confidence interval +/- 0.053) could be demonstrated in the perilymph. It can be concluded that ciprofloxacin has no ototoxic effect when administered systemically. Furthermore, when locally applied into the middle ear, it has the capacity to pass into the inner ear.

Animals↗
PubMed1992

Efficacy and tolerance of roxithromycin in comparison with erythromycin stearate in patients with lower respiratory tract infections.

The efficacy and tolerance of roxithromycin 150 mg b.i.d. were compared with those of erythromycin stearate 500 mg b.i.d. in patients with lower respiratory tract infections. Out of 86 patients recruited for the study, 79 were evaluable for tolerance and 76 for efficacy. These patients were evenly distributed among the 3 investigational clinics, with 26, 25 and 28 patients, respectively. The diagnosis of lower respiratory tract infections was based on clinical, laboratory, radiological and/or physical findings and, when available, bacteriological and serological findings. The duration of treatment was 10 days, with follow-up at post-treatment visits directly after treatment and 6 weeks thereafter. The clinical outcome was satisfactory with no significant difference between the drugs. More patients reporting adverse events were on erythromycin than on roxithromycin (51.3% vs 17.5%; p = 0.003). The results suggest that roxithromycin is as effective as erythromycin stearate in the treatment of lower respiratory tract infections and causes fewer adverse effects.

Adult↗
PubMed1991

Pharmacokinetics of meropenem compared to imipenem-cilastatin in young, healthy males.

Imipenem combined with cilastatin and meropenem was given as intravenous infusions of 1 g to eight young, healthy males on two separate occasions. Blood and urine samples were collected for up to 12 h. The terminal half-lives in plasma were 0.98 h and 1.11 h for meropenem and imipenem, respectively. The volume of distribution was smaller for meropenem than for imipenem (12.5 l and 14.4 l, respectively). The plasma clearance for meropenem was 188 (SD 31) ml/min and for imipenem 183 (SD 25) ml/min. Renal clearance was on average 139 (SD 24) ml/min and 135 (SD 11) ml/min, respectively. About 75% of the administered dose of both compounds was eliminated unchanged in urine. Non-renal clearance accounted for approximately 25% of the total clearance for both drugs. The kinetics of meropenem are very similar to those of imipenem given with cilastatin, and meropenem is as stable against renal metabolic degradation as imipenem combined with cilastatin.

Adult↗
PubMed1991

Pharmacokinetics of meropenem and its metabolite ICI 213,689 in healthy subjects with known renal metabolism of imipenem.

Six healthy male subjects who had received imipenem without cilastatin in previous studies, were given 500 mg meropenem as single 30 min intravenous infusions. Plasma and urine samples were collected for 12 h and meropenem and its metabolite were assayed by HPLC and RIA, respectively. The mean plasma half-life of meropenem was 0.8 h, mean plasma clearance 277 ml/min and the mean volume of distribution 20.4 l. The metabolite reached mean peak plasma concentrations of 1.5 mg/l. Renal clearance of meropenem averaged 200 ml/min. The mean urinary recovery of the metabolite was 20% and of unchanged drug 72% of the dose given. The recovery of meropenem ranged from 62.2% to 78.2% and was correlated to the urinary recovery of imipenem when given without cilastatin to the same subjects in previous studies (range 15.2-32.2%, rank correlation coefficient = 0.934). The results indicate that meropenem is much less susceptible to renal metabolism than imipenem. The inter-subject variability observed with meropenem correlates with the extent of urinary recovery of imipenem observed in previous studies with imipenem alone, indicating some susceptibility of meropenem to renal dehydropeptidase-I.

Adult↗
PubMed1990

Changes in plasma lipoproteins in acute malaria.

Plasma lipid and lipoprotein concentrations were monitored in 16 patients with acute malaria. Plasma high density lipoprotein (HDL) levels decreased dramatically during the first 3 d after diagnosis to around 0.2 mmol l-1 (reference range 0.8-1.6 mmol l-1). The low HDL levels were related to parasitaemia, and rapidly recovered after successful therapy. Plasma triglyceride concentrations were moderately increased and plasma low density lipoprotein (LDL) cholesterol concentrations decreased during the course of infection. The mechanisms underlying the selective and pronounced decline in HDL cholesterol concentration remain obscure, but the reproducible phenomenon may be useful as an additional diagnostic tool in suspected malaria infection.

Acute Disease↗
PubMed1990

Influence of ciprofloxacin on the colonic microflora in young and elderly volunteers: no impact of the altered drug absorption.

The colonic microflora was studied before, on the fifth day of dosing, and 2 weeks after a 5-day oral course of ciprofloxacin 500 mg BID given to 7 young and 7 elderly, healthy volunteers. Considerable changes in the aerobic microflora were found, while the effects on the anaerobic bacteria were less pronounced. Despite larger absolute bioavailability of the first dose in the elderly (77 vs. 63%; p less than 0.05), the effect of ciprofloxacin on the microflora was similar in the two groups of volunteers. A higher number of clostridia were detected in faeces from elderly subjects before, during, and after the ciprofloxacin regimen.

Administration, Oral↗
PubMed1989

Pharmacokinetics of ciprofloxacin in the elderly: increased oral bioavailability and reduced renal clearance.

The pharmacokinetics of ciprofloxacin was studied after single intravenous and oral doses of 250 mg and during and after a five-day oral regimen of 500 mg twice daily in eight young (22-34 years) and eight elderly (63-76 years), healthy male volunteers. The absolute bioavailability of an oral dose was greater in the elderly than in the young subjects at both 250 mg (72 versus 58%; p less than 0.05) and 500 mg (79 versus 63%; p less than 0.05). Distribution was unaffected by age. The physiological aging of the kidneys resulted in a reduced renal clearance, while no significant changes in non-renal clearance, total clearance and terminal half-life were found in the elderly. The age-related increase in the bioavailability of ciprofloxacin, whether due to facilitated absorption and/or reduced first-pass elimination, is a hitherto unique finding for antibiotics. As a consequence, reduction of orally administered doses of ciprofloxacin should be considered for elderly patients.

Administration, Oral↗
PubMed1989

Age dependence of renal function: clearance of iohexol and p-amino hippurate in healthy males.

Iohexol, a newly developed non-ionic contrast agent, has been recently documented as a reliable glomerular filtration marker. This study describes the age dependence of the single injection clearance of iohexol in a sample of healthy male volunteers ranging from 21 to 77 years of age. In parallel, renal plasma flow was studied by measuring the total clearance of p-amino hippuric acid administered as a continuous infusion. In subjects older than 50 years a negative correlation to age was found for both p-amino hippuric acid and iohexol clearance, with a reduction of 52 ml/min and 12 ml/min per decade, respectively, whereas no age dependence was found for younger subjects. Correlation between p-amino hippuric acid and iohexol clearances was 0.81. However, the filtration fraction, defined as the ratio of iohexol to p-amino hippuric acid clearance, was higher in the elderly subjects. A consistent discrepancy was found between total and renal clearances of p-amino hippuric acid, indicating significant renal metabolism. Renal clearance of creatinine was poorly correlated to iohexol clearance and did not show any relationship to age.

Adult↗
PubMed1989

Advancing age and acute infection influence the kinetics of ceftazidime.

The pharmacokinetics of ceftazidime were studied after single intravenous injections of 2 g in 10 healthy, elderly male volunteers (63-76 years old). None of the subjects were on concurrent drug treatment and all had normal age-correlated glomerular filtration rate. Mean values for major pharmacokinetic variables were: terminal half-life 2.63 h, area under the serum concentration curve 417.6 h mg/l, total clearance 74.6 ml/(min 1.73 m2), renal clearance 53.6 ml/(min 1.73 m2), urinary recovery/12 h 71.7% of dose and apparent volume of distribution (Vss) 15.0 l/1.73 m2. Data were compared with our earlier findings in studies of young male volunteers and elderly, acutely ill male patients. Advanced age was accompanied by a reduction in clearance of ceftazidime, while no significant age-related changes in distribution were noted. Acute infection was associated with increased Vss and enhanced renal clearance; alterations possibly caused by fever-induced changes in vascular permeability and renal blood-flow.

Acute Disease↗
PubMed1989

Influence of age on the pharmacokinetics of ciprofloxacin.

Data from 4 previously published reports on kinetics after oral ciprofloxacin administration are reviewed. Preliminary results from a study with oral and intravenous administration in elderly and young, healthy males are presented. The total clearance of ciprofloxacin is maintained in the elderly, while the renal clearance is reduced as a consequence of the age-related, physiological reduction of kidney functions. After oral administration there is, furthermore, an increased AUC and Cmax, which are explained by a higher bioavailability of an oral dose in the elderly (72.4%) as compared to young volunteers (58.4%).

Administration, Oral↗
PubMed1989

Comparison of efficacy and tolerance of intravenously and orally administered ciprofloxacin in cystic fibrosis patients with acute exacerbations of lung infection.

Twenty patients (17-27 yr) with cystic fibrosis were given ciprofloxacin at 30 pulmonary infectious exacerbations. All patients were chronically colonized with Pseudomonas aeruginosa. Twenty-five courses were completed, 13 orally (15 mg/kg b.i.d.) and 12 intravenously (4-6 mg/kg b.i.d.). Clinical efficacy was excellent or good in 85-90% of the courses and growth of P. aeruginosa was markedly reduced in 33-46%. Body weight and clinical score improved significantly. White blood cell count decreased and pulmonary function was improved. Reversible adverse effects, mainly rash and urticaria, appeared at seven occasions, five severe enough to cause interruption of treatment. Clinical efficacy and tolerance were better with oral than intravenous administration at the dosages used in this study. Excellent bioavailability provides additional basis for oral treatment with ciprofloxacin in cystic fibrosis patients.

Administration, Oral↗
PubMed1988

Influence of age on the pharmacokinetics of ceftazidime in acutely ill, adult patients.

The single and multiple i.v. dose pharmacokinetics of ceftazidime were investigated in 37 acutely ill patients with normal age-related glomerular function. Distribution was rapid with similar t1/2 alpha at all ages. Compared to the younger patients, elderly subjects had lower total and renal clearances and reduced urinary recovery. Ceftazidime clearance was closely correlated with glomerular function. The t1/2 beta was approximately 2 h in young and middle-aged patients, 2.73 h in patients aged 60-79 years, and 3.54 h in those above 80 years. The AUC was more than doubled in the oldest patients compared to individuals younger than 40 years. Vss did not change with advancing age, but was larger than previously reported in healthy volunteers. Elimination variables were not altered during multiple dosing, but a small but significant increase in AUC was detected in the elderly. Dose reduction by 50% in patients more than 70 years old is suggested.

Acute Disease↗
PubMed1988

Comparative pharmacokinetics of ceftazidime in young, healthy and elderly, acutely ill males.

The pharmacokinetics of ceftazidime have been investigated after single and multiple i.v. doses in 9 young healthy male volunteers and 15 elderly male patients with acute bacterial infections. All subjects had normal, age-correlated glomerular function. Distribution and elimination in young volunteers were unaffected by posture and were similar to what has been reported earlier. In contrast, elderly patients had longer t1/2 beta (3.1 vs 1.9 h), larger AUC (414.0 vs 276.6 h.mg/l), lower total and renal clearances, reduced urinary recovery over 12 h and enlarged Vss. Total serum clearance of ceftazidime was closely correlated with the 51Cr-EDTA clearance. There was no significant change in 51Cr-EDTA clearance after seven days of treatment. A reduction in the dose of beta-lactam antibiotics eliminated by the kidney is advisable in elderly patients with an acute bacterial infection.

Acute Disease↗
PubMed1988

Pharmacokinetics of intravenous ciprofloxacin at three different doses.

The pharmacokinetics of ciprofloxacin were evaluated after single iv bolus injections of 50, 100 and 250 mg in eight young, healthy male volunteers. Concentrations were determined by high-performance liquid chromatography. The mean terminal half-life was 3.33, 3.73 and 3.45 h for 50, 100 and 250 mg doses, respectively. No significant differences between the three dose levels were noted for terminal half-life, total and renal clearances, distribution volume (Vd(ss] and percentage of dose recovered in urine over 24 h. The areas under the serum concentration curves were proportional to the given dose. We conclude that distribution and elimination of ciprofloxacin is not dose dependent.

Adult↗
PubMed1988

Magnetic resonance imaging in the diagnosis of spinal epidural abscess.

In 3 patients with epidural abscess, 2 in the cervical spine and 1 in the lumbar spine the definite diagnosis was established by magnetic resonance imaging (MR). In 1 patient computerized tomography was performed but the correct diagnosis was revealed only by MR. The infections were all acute and due to Staphylococcus aureus organisms. One patient developed a tetraparesis on the third day, before the diagnosis was established or antibiotic treatment initiated. The other 2 showed only minor and passing neurologic deficits. None was subjected to laminectomy. In 2 cases the diagnosis was confirmed by puncture. None of the patients had a preceding trauma or a known focus for the staphylococcal infection.

Abscess↗