Survival outcomes of alternate dosing schedule of pemetrexed as maintenance therapy in NSCLC: Single institution experience.

Background: Maintenance therapy with pemetrexed has shown survival benefit in patients with advanced stage non-small cell lung cancer (NSCLC). The recommended dose schedule is 500 mg/m 2 in 21-day cycles. Prolonged treatment with maintenance pemetrexed can result in cumulative toxicities.

Safety of Same-Day Vitamin B12 Supplementation in Patients Receiving Pemetrexed for the Treatment of Non-Small-Cell Lung Cancer or Pleural Mesothelioma: A Retrospective Analysis.

Background: Pemetrexed is a folate analog inhibitor for the treatment of non-small-cell lung cancer (NSCLC) and malignant pleural mesothelioma. Folic acid and vitamin B12 supplementation before initiating pemetrexed is necessary because of high rates of cytopenias without supplementation. However, the timing of supplementation has not been thoroughly investigated.

Metformin and Not Diabetes Influences the Survival of Resected Early Stage NSCLC Patients.

Background: Published data suggest that diabetes influences survival of patients with lung cancer. The anti-cancer effect of metformin confounds this association. We sought to study the association of diabetes and metformin with survival in patients undergoing resection of stage I non-small cell lung cancer (NSCLC).

Exposure-response analyses of tigecycline tolerability in healthy subjects.

Tigecycline exposure (area under the concentration-time curve [AUC((0-infinity))] and maximum serum concentration [C(max)]) and first occurrence of nausea and vomiting were evaluated in 136 healthy subjects after 12.5- to 300-mg single doses. Nausea was more frequent in females (46%, 10/22) compared with males (31%, 11/36) after 100-mg doses.

Application of patient population-derived pharmacokinetic-pharmacodynamic relationships to tigecycline breakpoint determination for staphylococci and streptococci.

Correctly determined susceptibility breakpoints are important to both the individual patient and to society at large. A previously derived patient population pharmacokinetic model and Monte Carlo simulation (9999 patients) were used to create a likelihood distribution of tigecycline exposure, as measured by the area under the concentration-time curve at 24 h (AUC(24)). Each resultant AUC(24) value was paired with a clinically relevant fixed MIC value ranging from 0.

Use of a clinically derived exposure-response relationship to evaluate potential tigecycline-Enterobacteriaceae susceptibility breakpoints.

Potential tigecycline-Enterobacteriaceae susceptibility breakpoints were evaluated using 2 approaches, which differed in the nature of the probabilities assessed by MIC value. Using a previously derived tigecycline population pharmacokinetic model and Monte Carlo simulation, a probability density function of steady-state area under the concentration-time curve for 24 h (AUC(SS(0-24))) values for 9999 patients was generated. AUC(SS(0-24)) values were divided by clinically relevant fixed MIC values to derive AUC(SS(0-24))/MIC ratios, which were used to calculate the clinical response expectation by MIC value based upon a logistic regression model for efficacy (1st approach).

Pharmacokinetic/pharmacodynamic profile for tigecycline-a new glycylcycline antimicrobial agent.

Tigecycline is a new first-in-class glycylcycline antimicrobial agent with expanded broad-spectrum activity against both Gram-negative and Gram-positive aerobes and anaerobes, as well as atypical bacterial species. The spectrum of activity extends to clinically relevant susceptible and multidrug-resistant strains of Staphylococcus aureus, Streptococcus pneumoniae, vancomycin-resistant enterococci, and Enterobacteriaceae, including extended-spectrum beta-lactamase-producing strains. Tigecycline is administered as an intravenous formulation and has been studied in the treatment of serious polymicrobial infections, including complicated skin and skin-structure infections and intra-abdominal infections.

The pharmacokinetic and pharmacodynamic profile of tigecycline.

Tigecycline, a first-in-class expanded-spectrum antimicrobial agent, has demonstrated efficacy in the treatment of complicated intra-abdominal and skin and skin-structure infections. This new antibiotic is available as an intravenous formulation and exhibits linear pharmacokinetics. It is rapidly distributed and has a large volume of distribution, indicating extensive tissue penetration.

Novel pharmacokinetic-pharmacodynamic model for prediction of outcomes with an extended-release formulation of ciprofloxacin.

The pharmacokinetics of an extended-release (XR) formulation of ciprofloxacin has been compared to that of the immediate-release (IR) product in healthy volunteers. The only significant difference in pharmacokinetic parameters between the two formulations was seen in the rate constant of absorption, which was approximately 50% greater with the IR formulation. The geometric mean plasma ciprofloxacin concentrations were applied to an in vitro pharmacokinetic-pharmacodynamic model exposing three different clinical strains of Escherichia coli (MICs, 0.

Clinical pharmacodynamics of linezolid in seriously ill patients treated in a compassionate use programme.

Objective: To characterise the pharmacokinetic-pharmacodynamic relationships for linezolid efficacy.

Design And Study Population: Retrospective nonblinded analysis of severely debilitated adult patients with numerous comorbid conditions and complicated infections enrolled under the manufacturer's compassionate use programme.

Methods: Patients received intravenous or oral linezolid 600 mg every 12 hours.

Fluoroquinolone AUIC break points and the link to bacterial killing rates. Part 2: human trials.

Objective: To review clinical trials with fluoroquinolones and the pharmacokinetic and pharmacodynamic parameters predictive of clinical and microbiologic outcomes and resistance. Data on fluoroquinolones are summarized and the premise that a single AUIC target >125 may be used for all fluoroquinolones against all target organisms is examined.

Data Sources: Primary articles were identified by a MEDLINE search (1966-February 2002) and through secondary sources.

Fluoroquinolone AUIC break points and the link to bacterial killing rates. Part 1: In vitro and animal models.

Objective: To review in vitro and animal model studies with fluoroquinolones and the pharmacokinetic and pharmacodynamic relationships that are predictive of clinical and microbiologic outcomes and resistance. Data on fluoroquinolones are summarized and examine the premise that a single area under the inhibitory concentration-time curve (AUIC) target >125 may be used for all fluoroquinolones with concentration-dependent killing actions and against all target organisms.

Data Sources: Primary articles were identified by MEDLINE search (1966-February 2002) and through secondary sources.

Population pharmacokinetics of linezolid in patients treated in a compassionate-use program.

Data obtained from 318 adult patients treated under the linezolid compassionate-use protocol were used to develop a population model of the pharmacokinetics of intravenous and oral linezolid. All of the patients received 600 mg of linezolid every 12 h, intravenously and/or orally. Blood samples (2 to 10 per patient; median, 4) were obtained and assayed for linezolid by high-performance liquid chromatography.

Linezolid for the treatment of multidrug-resistant, gram-positive infections: experience from a compassionate-use program.

Linezolid was provided for treatment of multidrug-resistant, gram-positive infections through a compassionate-use program. Patients (n=796) received 600 mg of linezolid intravenously or orally every 12 h (828 treatment courses). Bacteremia was present in 46% of infections, endocarditis was present in 10.

Successful treatment of methicillin-resistant Staphylococcus aureus pulmonary infection with linezolid in a patient with cystic fibrosis.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of pulmonary infection in patients with cystic fibrosis (CF). Because these organisms are frequently multidrug-resistant, most patients require intravenous therapy with vancomycin. We report on the first case of successful treatment of a pulmonary exacerbation due to MRSA in a CF patient with a new antimicrobial, linezolid.