Lack of effect of food on the bioavailability of a new ketolide antibacterial, telithromycin.

Telithromycin is an innovative antibacterial designed for the treatment of community-acquired respiratory tract infections. This study assessed the effect of food on the bioavailability of a single oral dose of telithromycin 800 mg in healthy male subjects. Male volunteers aged 18-45 y were recruited for an open-label, single-dose, 2-period, cross-over study.

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 View Article and Find Full Text PDF

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.

HT29-MTX and Caco-2/TC7 monolayers as predictive models for human intestinal absorption: role of the mucus layer.

The permeability of 19 compounds in both the Caco-2/TC7 and HT29-MTX models was determined, and the ability of each model to predict intestinal absorption in humans was compared. Similar apparent permeability values (log P(app)) were obtained in both models for the majority of compounds tested, and plots of log P(app) versus fraction absorbed in humans gave comparable sigmoidal curves. A linear correlation was also observed between the log P(app) values derived from these two models, which suggests that HT29-MTX is an alternative model for absorption prediction in humans.

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.

Absorption of angiotensin II antagonists in Ussing chambers, Caco-2, perfused jejunum loop and in vivo: importance of drug ionisation in the in vitro prediction of in vivo absorption.

The aims of this study were (i) to compare the absorption of three closely related inhibitors of angiotensin II, RU60018, RU60079 and HR720, in various in vitro and in vivo models, and (ii) to explain the differences in the results and to assess the importance of drug ionisation to predict absorption. Drug absorption was investigated in Ussing chambers, Caco-2 cell monolayers, perfused rat jejunum loops and in vivo after oral, intraduodenal or intravenous administration. In Ussing chambers, the analogues showed the same site-related absorption profile and a common mechanism involving the paracellular pathway.

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.

Concentrations of cefpodoxime in plasma, adenoid, and tonsillar tissue after repeated administrations of cefpodoxime proxetil in children.

Cefpodoxime proxetil was administered to 36 children undergoing tonsillectomy, adenoidectomy or both. It was very well tolerated. The detectable tissue concentrations of cefpodoxime were moderate but remained constant (approximately 0.

Pharmacokinetics of cefodizime following single doses of 0.5, 1.0, 2.0, and 3.0 grams administered intravenously to healthy volunteers.

Cefodizime is a new expanded-spectrum cephalosporin for parenteral use which possesses a broad antibacterial spectrum and potent antibacterial activity and is stable against most beta-lactamases. The aim of this study was to assess the pharmacokinetics of cefodizime, administered intravenously, over the dose range of 0.5 to 3.

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)].

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.

Trandolapril: pharmacokinetics of single oral doses in healthy male volunteers.

The pharmacokinetics and dose proportionality of trandolapril, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated in 12 healthy male volunteers in a four-way randomized crossover study over the therapeutic dose range, 0.5-4 mg. Trandolapril is rapidly absorbed, with a single elimination half-life (t1/2) of 0.

Diffusion of cefpirome into the cerebrospinal fluid of patients with purulent meningitis.

We evaluated the diffusion of cefpirome into the cerebrospinal fluid (CSF) of 25 patients with bacterial meningitis or ventriculitis who were receiving conventional antibiotic treatment. A single cefpirome dose of 2 g was infused at day 2-3 after the onset of therapy. Concentrations of cefpirome in serum and CSF obtained at 2, 4, 8 or 12 h after the infusion were determined by high-performance liquid chromatography.

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.

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.

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.

Multiple dose pharmacokinetics of cefpodoxime in young adult and elderly patients.

Multiple dose pharmacokinetics of a new third-generation cephalosporin, cefpodoxime, were evaluated in adults (15, 18-60 years) and elderly adults (10, greater than or equal to 70 years), all out-patients suffering from acute lower respiratory tract infection. A dose of 200 mg cefpodoxime proxetil (expressed in mg cefpodoxime) was administered 12-hourly for seven to ten days and timed blood samples were evaluated on days 0, 3, 5, 6/7 and on the last day of treatment. Results showed that the pharmacokinetics in adult and elderly patients were comparable with those of healthy volunteers and with each other, with the exception of one elderly patient with severe renal impairment.

Pharmacokinetics of cefpodoxime in young and elderly volunteers after single doses.

Three pharmacokinetic studies involving single oral doses of cefpodoxime proxetil in healthy volunteers are reported. The first study was to determine the absolute bioavailability of cefpodoxime, the second was to study the relationship between the oral dose of cefpodoxime proxetil and pharmacokinetic parameters of cefpodoxime, and the third was to compare the pharmacokinetics of cefpodoxime in healthy young and elderly volunteers. Half the dose of cefpodoxime orally administered as cefpodoxime proxetil in tablet form reaches the systemic circulation, while 80% of the cefpodoxime absorbed is excreted unchanged in urine.

Pharmacokinetics of cefodizime in the elderly following single and repeated intravenous administration of 1 g.

In an open, crossover study of 12 patients of mean age 74 (range 64-88) who required perioperative prophylactic antibiotic therapy, cefodizime was administered as a single iv infusion of 1 g, and repeated infusions of 1 g twice daily for 4.5 days. Serum and urine concentrations of cefodizime were determined by high performance liquid chromatography.

Pharmacokinetics of cefodizime administered intravenously as a single-dose (1.0 and 2.0 g) to healthy adult volunteers.

Cefodizime is a new third generation cephalosporin for parenteral use. The purpose of this study was to define the pharmacokinetic profile of cefodizime after intravenous dosing with 1.0 and 2.

The pharmacokinetics of cefodizime following intravenous and intramuscular administration of a single dose of 1.0 g.

The pharmacokinetics and absolute bioavailability of cefodizime were determined after iv and im administration of a single 1.0 g dose in eight healthy volunteers. The absolute bioavailability of cefodizime after im injection of 1.

Recombinant human gamma-interferon in patients with chronic active hepatitis B: pharmacokinetics, tolerance and biological effects.

Pharmacokinetics, tolerance and biological effects of human recombinant gamma-interferon were studied in 12 patients with chronic active hepatitis B. Serum concentrations of gamma-interferon were measured by radioimmunoassay in four patients after a subcutaneous injection of 10 million U (0.5 mg); the peak serum concentration of gamma-interferon (29 +/- 7 U/ml) was reached after 5 to 8 hr and gamma-interferon remained detectable for 24 to 36 hr.

Captopril/hydrochlorothiazide combination in elderly patients with mild-moderate hypertension. A double-blind, randomized, placebo-controlled study.

Fifty-six elderly patients (mean age 72.1 +/- 4.1 years; mean creatinine 111.

Alternating radiotherapy and chemotherapy schedules in small cell lung cancer, limited disease.

Sixty-three evaluable patients with limited small cell lung carcinoma were entered into two pilot studies alternating 6 cycles of combination chemotherapy (Doxorubicin 40 mg/m2 d 1; VP16213 75 mg/m2 d 1, 2, 3; Cyclophosphamide 300 mg/m2 d 3, 4, 5, 6; and Methotrexate 400 mg/m2 d 2--plus folinic acid rescue--or Cis-Platinum 100 mg/m2 d 2) with 3 courses of mediastinal radiotherapy as induction treatment. The first course of radiotherapy started 10 days after the second cycle of chemotherapy; there was a 7 day rest between chemotherapy and radiotherapy courses. This 6 month induction treatment was followed by a maintenance chemotherapy.

[Alternating chemotherapy and radiotherapy in the induction treatment of small cell bronchial carcinoma (forms limited to the thorax)].

Sixty three patients with limited small cell lung carcinoma were entered into a pilot study alternating monthly cycles of combination chemotherapy (doxorubicin, VP16213, cyclophosphamide and methotrexate (group A) or cis platinum (group B) with 3 courses of mediastinal radiotherapy. The total mediastinal dose was 45 Gy for the first 28 patients (group A) and 55 Gy for the remaining 35 (group B). The complete response rate was 86% in group A (median survival 14 months) and 91% in group B (median survival 20 months).