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E Sultan

Publications and source records attributed to E Sultan.

16 recordsLinked to original sources
PubMed2003

Telithromycin (HMR 3647) achieves high and sustained concentrations in tonsils of patients undergoing tonsillectomy.

Telithromycin, the first ketolide antimicrobial to be developed for clinical use, has potent activity against group A beta-haemolytic streptococci (GABHS), including macrolide-resistant strains. The penetration of telithromycin into tonsils was assessed in 22 adults undergoing tonsillectomy at 3, 12 or 24 h after the fourth dose of oral telithromycin 800 mg once daily. Telithromycin rapidly penetrated tonsillar tissues, achieving a mean concentration of 3.95 mg/kg at 3 h post dose, 3.4 times greater than the corresponding plasma concentration (1.22 mg/l. The mean tonsil:plasma concentration ratio increased to 13.1 at 24 h post dose, indicating slower elimination from tonsils than plasma. Tonsillar and plasma concentrations exceeded the MIC(50) for GABHS throughout the 24-h dosing period. These findings suggest that telithromycin may be an effective new alternative treatment for GABHS tonsillopharyngitis.

Administration, Oral↗
PubMed2003

Pharmacokinetics of the ketolide telithromycin after single and repeated doses in patients with hepatic impairment.

The pharmacokinetic profiles of single and repeated oral doses of telithromycin 800 mg/day were compared in patients with hepatic impairment and healthy subjects in two open-label, non-randomized, parallel-group, multicentre studies. The maximal plasma concentrations (Cmax) and the area under the plasma concentration-time (AUC) curves for telithromycin were similar in hepatically impaired patients and healthy subjects in the single- and repeated-dose studies. The extent of formation of RU 76363, the major circulating metabolite of telithromycin, was decreased following single and repeated doses in patients with hepatic impairment compared with healthy subjects. In the single-dose study, the Cmax of RU 76363 was 2-fold lower (P<0.01) and the initial elimination half-life (t(1/2lambda1)) was 44% higher (P<0.01). The Cmax and AUC from 0 to 24 h post-dose were approximately 50% lower on Day 1 (P< or =0.01) and Day 7 (P< or =0.001) in the repeated-dose study. The terminal elimination half-life (t(1/2lambdaz)) of telithromycin was 1.4-fold higher (P<0.001) in the hepatically impaired patients compared with the healthy subjects in the single-dose study. However, t(1/2lambda1) and t(1/2lambdaz) were similar after repeated doses in both populations, suggesting that the decrease in formation of RU 76363 is compensated by an increase in clearance via other pathways. Telithromycin 800 mg was well tolerated in both populations. In conclusion, a once-daily dose of telithromycin is well tolerated in patients with hepatic impairment. Exposure to telithromycin was comparable in patients with hepatic impairment and healthy subjects and thus, no dosage adjustment is required in this patient group providing renal function is not severely impaired.

Administration, Oral↗
PubMed2002

Penetration of telithromycin (HMR 3647), a new ketolide antimicrobial, into inflammatory blister fluid following oral administration.

The penetration of telithromycin (HMR 3647), a novel ketolide antimicrobial, has been assessed in an open, single-dose study in eight healthy male subjects. Following a single, oral, 600 mg dose the mean ratio of the concentration of telithromycin in blister fluid over plasma was 1.38. Significant blister fluid concentrations were maintained up to 24 h post-dose. These results indicate that telithromycin penetrates well into inflammatory extracellular fluid, achieving high and sustained concentrations in this medium.

Administration, Oral↗
PubMed2002

Pharmacokinetics and absolute oral bioavailability of an 800-mg oral dose of telithromycin in healthy young and elderly volunteers.

BACKGROUND: This two-way, randomized, single-dose, crossover study determined the pharmacokinetics and absolute oral bioavailability of telithromycin in young and elderly healthy subjects. METHODS: Twelve young (18-40 years) and 12 elderly (>65 years and </=85 years) subjects received a single 800-mg oral dose of telithromycin or an intravenous infusion of 400 mg (young subjects) or 480 mg (elderly subjects) of telithromycin over 2.5 h in two treatment periods, separated by a 1-week washout period. The plasma concentrations and pharmacokinetic parameters of telithromycin and its major metabolite, RU 76363, were determined. Absolute oral bioavailability was calculated using the area under the plasma concentration-time curve (AUC) from zero hours to infinity. RESULTS: The absolute oral bioavailability of telithromycin was 57% in both young and elderly subjects. The AUC for the metabolite was lower after intravenous infusion of telithromycin, indicating first-pass loss following oral administration. Telithromycin was well tolerated in both groups of subjects. CONCLUSIONS: Telithromycin has an absolute oral bioavailability of 57% in young and elderly subjects and is well tolerated.

Administration, Oral↗
PubMed2001

Pharmacokinetics of the new ketolide telithromycin (HMR 3647) administered in ascending single and multiple doses.

Telithromycin (HMR 3647) is a novel ketolide antimicrobial with good activity against both common and atypical respiratory pathogens, including many resistant strains. This randomized, three-period crossover study determined the dose proportionality of telithromycin pharmacokinetics after single and multiple dosing in healthy subjects. In each treatment period, subjects received a single oral dose of 400, 800 or 1,600 mg of telithromycin followed 4 days later by the same dose once daily for 7 days. Blood and urine samples were taken throughout the study for determination of pharmacokinetic parameters for telithromycin and RU 76363, its main metabolite. Telithromycin and RU 76363 achieved steady state within 2 to 3 days of once-daily dosing. A slight accumulation of telithromycin was observed after 7 days of therapy, with values of the area under the concentration-time curve from 0 to 24 h approximately 1.5 times higher than those achieved with the single dose. The pharmacokinetics of telithromycin and RU 76363 deviated moderately from dose proportionality. At a dose of 800 mg/day, telithromycin attained mean maximal and trough plasma concentrations of 2.27 and 0. 070 mg/liter respectively. Elimination was biphasic; initial and terminal half-lives were 2.87 and 9.81 h for the 800-mg dose. Study medication was well tolerated, although adverse events tended to be more frequent at the 1,600-mg dose. This study showed that telithromycin was generally well tolerated and suggests that a once-daily 800-mg oral dose of telithromycin maintains an effective concentration in plasma for the treatment of respiratory tract infections involving the key respiratory pathogens.

Adolescent↗
PubMed1999

Celebrity dreams.

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Anniversaries and Special Events↗
PubMed1998

Concentrations of cefpirome in cerebrospinal fluid of children with bacterial meningitis after a single intravenous dose.

A single intravenous dose of cefpirome, 50 mg/kg, was administered to 15 children with bacterial meningitis 24 to 48 h after initiation of standard antibiotic and steroid therapy. Cefpirome concentrations in serum and cerebrospinal fluid were determined at selected time intervals. The mean (standard deviation) peak concentration in cerebrospinal fluid (n = 5) was 10.8 (7.8) microg/ml. Drug concentrations in cerebrospinal fluid above the MIC for Streptococcus pneumoniae at which 90% of the isolates were inhibited were found 2, 4, and 8 h after the dose of cefpirome was given. The penetration of cefpirome into cerebrospinal fluid compares favorably with that of other extended-spectrum cephalosporins and suggests that this agent would be useful in the therapy of childhood meningitis, including cases caused by drug-resistant S. pneumoniae.

Cephalosporins↗
PubMed1994

Pharmacokinetics and pharmacodynamics of trandolapril after repeated administration of 2 mg to young and elderly patients with mild-to-moderate hypertension.

The new angiotensin-converting enzyme (ACE) inhibitor trandolapril 2 mg was administered daily for 10 consecutive days to young (mean age +/- SEM 44.1 +/- 2.3 years; n = 10) and elderly (mean age +/- SEM 69.3 +/- 0.9 years; n = 14) patients with mild-to-moderate hypertension. All groups had similar baseline blood pressures: mean 164/100 mm Hg. Maximal plasma ACE inhibition on day 10 and residual inhibition 24 h after the last dose was the same, irrespective of age: young, 85.2 and 57.4%; elderly 89.1 and 59.8%, respectively. There was no difference between the results on day 1 for the young and elderly groups. The absorption of trandolapril was rapid (< 1 h in all groups). The peak plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were slightly higher in the older group, but the elimination half-life (t1/2) was the same, with no accumulation after repeat dosing. A steady-state plasma concentration of the active metabolite of trandolapril, trandolaprilat, was reached after 4 days in the two groups, with similar accumulation ratios (young, 1.48; elderly, 1.49). At steady state, the Cmax and AUC 0-24 h for trandolaprilat were similar in the two groups: young, 7.49 +/- 0.98 ng/ml and 82.27 +/- 6.95 ng/ml/h; elderly, 8.35 +/- 0.67 ng/ml/h and 96.75 +/- 5.67 ng/ml/h. Maximal reductions in systolic/diastolic blood pressures (at 6 h postdose) were -14.1%/-16.1% in young patients and -14.6%/-17.5% for the elderly. Significant blood pressure reduction persisted for 48 h after the last dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pharmacokinetics and pharmacodynamics of trandolapril after repeated administration of 2 mg to patients with chronic renal failure and healthy control subjects.

A new, long-acting angiotensin-converting enzyme (ACE) inhibitor, trandolapril, was administered daily for 10 days to 13 patients with chronic renal failure [CRF; creatinine clearance (CLCR) 7-55 ml/min/1.73 m2) and 8 healthy volunteers (CLCR > 80 ml/min/1.73 m2)]. Plasma ACE inhibition parameters were the same, irrespective of the degree of renal insufficiency, although renal failure tended to prolong ACE inhibition. The pharmacokinetics of trandolapril were not affected by CRF; hence, no accumulation of trandolapril was detected. After single or repeated administration the active metabolite, trandolaprilat, showed an inverse correlation between maximal plasma concentrations (Cmax) and CLCR (r = -0.676 day 1 and r = -0.864 day 10) and area under the concentration-time curve (AUC) and CLCR (r = -0.635 day 1 and r = -0.794 day 10). The renal clearance of trandolaprilat showed significant linear correlation (r = > 0.885, p < 0.0001) with CLCR after single (r = 0.879) and repeated administration (r = 0.957). Significantly reduced excretion of trandolaprilat was seen only when the CLCR was < 30 ml/min/1.73 m2. A steady state had been achieved by 7 days in all patients, and extrapolation suggested that this was achieved in most cases after 4 days. The drug was well tolerated. The effect of CRF on the pharmacokinetics and pharmacodynamics of trandolaprilat is of significance only when CLCR is < 30 ml/min/1.73 m2. Hence, in these patients the standard dose should be reduced.

Adult↗
PubMed1991

[Pharmacokinetics of aspirin in African children with normal nutrition and malnutrition].

Pharmacokinetics of aspirin given orally at antipyretic dose (12 mg/kg) were studied in 11 African children aged 4-48 months. In order to examine the influence of nutritional status on aspirin kinetics, children were classified according to Waterlow criteria. Blood samples were collected during the 8 hours following the initial dose. Albumin, prealbumin and transferrin plasma levels were measured and plasma salicylic acid (SA) concentrations determined by a fluorometric method. Nutritional status seemed to have no prominent effect on plasma concentrations of SA. The volume of distribution found in our study was lower than those obtained in other studies. This could be explained by lower plasma aspirin esterase activities in black children. There were large individual variations in plasma salicylate concentrations. For example, even at antipyretic doses, saturation phenomena appeared in two children.

Aspirin↗
PubMed1990

Concentrations of cefpodoxime in plasma and lung tissue after a single oral dose of cefpodoxime proxetil.

Eighteen patients undergoing thoracotomy for suspected pulmonary neoplasia were given 200 mg cefpodoxime equivalent by mouth, before operation. Plasma samples were obtained before dose administration, and plasma and lung tissue samples were obtained at the time of operation which was 3, 6 or 12 h after the dose. All samples were assayed for cefpodoxime. The mean ratios for lung tissue/plasma concentrations were similar between 3 and 12 h after dose, suggesting that equilibrium between plasma and lung tissue concentrations was reached within 3 h of medication. The mean concentrations of cefpodoxime in lung tissue were 0.63 +/- 0.16, 0.52 +/- 0.09 and 0.19 +/- 0.02 mg/kg at 3, 6 and 12 h after administration, respectively. These observations indicate good, rapid and sustained penetration into lung tissue in concentrations greater than or equal to the MIC90 for most common micro-organisms found in community-acquired pneumonia.

Administration, Oral↗
PubMed1990

Concentrations of cefpodoxime in plasma and pleural fluid after a single oral dose of cefpodoxime proxetil.

Eighteen patients of either sex with pleural effusions underwent aspiration 3, 6 or 12 h after receiving a single oral dose of cefpodoxime proxetil equivalent to 200 mg cefpodoxime. The mean concentrations of cefpodoxime in pleural fluid were, respectively, 0.62, 1.84 and 0.78 mg/l for these three time intervals, the corresponding ratios between pleural fluid and plasma concentrations being 0.24, 0.67 and 1.07. The findings indicate that there is good penetration of cefpodoxime into pleural fluid. Concentrations between 3 and 12 h after dosing were equal to or above the MIC90 for most of the organisms commonly found in lower respiratory tract infections.

Administration, Oral↗
PubMed1990

Concentrations of cefpodoxime in plasma and tonsillar tissue after a single oral dose of cefpodoxime proxetil.

Seventeen patients undergoing tonsillectomy received cefpodoxime proxetil orally in a dose equivalent to 100 mg cefpodoxime 4, 7 or 12 h before operation. Plasma and tonsillar tissue concentrations of cefpodoxime were assayed by a microbiological method. Tonsillar tissue concentrations after 4 and 7 h were 0.24 and 0.09 mg/kg respectively--being 23% of the plasma concentration. The tonsillar tissue concentration after 12 h was less than 0.06 mg/kg. As the MIC for Streptococcus pyogenes is less than 0.06 mg/l, cefpodoxime proxetil may be of value in acute tonsillitis.

Administration, Oral↗
PubMed1990

Disposition of fleroxacin, a new trifluoroquinolone, and its metabolites. Pharmacokinetics in renal failure and influence of haemodialysis.

The pharmacokinetics of fleroxacin and its metabolites following a single oral dose of fleroxacin 400mg were examined in 6 healthy subjects and 24 patients with various degrees of renal insufficiency. Plasma and urine samples, collected at various times after administration, were assayed by high performance liquid chromatography (HPLC). In healthy subjects, Cmax was 6.8 +/- 0.7 mg/L; tmax = about 1h, t1/2 = 14 +/- 2h, total clearance = 4.86 +/- 0.72 L/h and the percentage of unchanged fleroxacin excreted in urine in 48 hours was 48 +/- 4% (HPLC). Plasma concentrations of metabolites were very low and accounted for no more than 5% of the levels of unchanged fleroxacin. In uraemic patients Cmax did not change, whatever the degree of renal failure; tmax was increased in patients with a glomerular filtration rate below 0.6 L/h, and Vd/f was independent of the severity of renal failure. These data suggest that bioavailability of the drug is unchanged. In uraemic patients t1/2 was prolonged and AUC multiplied by a factor of 2 to 3. A linear relationship was found between total and renal clearances of fleroxacin and creatinine clearance. Accumulation of N-demethyl-fleroxacin and N-oxide-fleroxacin was very high in uraemic patients, due to slow formation of these metabolites and decreased urinary elimination. Dialysance of fleroxacin and of its metabolites was approximately 3.6 to 4.8 L/h. These findings suggest that fleroxacin dosage may need to be reduced in patients with severe renal disease; in haemodialysed patients, treated every 2 days, a single dose of fleroxacin 400mg is recommended at the end of each dialysis session.

Adult↗
PubMed1988

Pharmacokinetics of pefloxacin and amikacin administered simultaneously to intensive care patients.

Ten adult patients with severe infections in an intensive care unit were treated simultaneously with 6 mg/kg pefloxacin and 7.5 mg/kg amikacin, infused i.v. over 1 h every 12 h for 5 days. Twelve h after the last infusion, pefloxacin alone was administered orally (400 mg tablet) every 12 h for 10 days. The pharmacokinetics of pefloxacin and its main metabolites, norfloxacin and pefloxacin N-oxide, were determined after the first (Day 1) and last (Day 5) infusions and after the last oral dose (Day 15). The kinetics of amikacin was determined after the first and the last infusion. The maximal and minimal steady-state plasma concentrations of amikacin were 27.3 and 3.3 mg/l. The total plasma clearance was 83.1 and 67.0 ml/min after the first and the last infusions, respectively, and the half-life was 3.9 and 5.0 h. The maximal and minimal steady-state plasma concentrations of pefloxacin were 13.1 and 7.9 mg/l after i.v. infusion and 13.4 and 9.0 mg/l after oral administration. Pefloxacin elimination (t1/2) increased from 11.3 h after the first infusion to 19.4 h after the last infusion and 21.1 h after the last oral dose. Total body clearance decreased from 90.8 (Day 1) to 51.9 (Day 5) and 56.4 ml/min (Day 15). The volume of distribution did not change significantly over the course of pefloxacin. Mean steady-state plasma concentrations of norfloxacin and pefloxacin N-oxide were respectively 0.5-0.6 mg/l and 0.9-1.3 mg/l after intravenous and oral administration of pefloxacin. There were no pharmacokinetic interaction between the drugs. The dosage regimen led to plasma concentrations of pefloxacin and amikacin within their therapeutic range.

Aged↗