The goals of this investigation were to illustrate the use of pharmacokinetic (PK)/pharmacodynamic (PD) modeling strategies in drug development based on a multiple-dose study of gefitinib in a preclinical tumor model. Mice bearing s.c. LN229-wild-type epidermal growth factor receptor or LN229-EGFRvIII mutant (a sensitizing mutation) tumors were administered gefitinib at oral doses of either 55 ...

OBJECTIVES To explore whether pharmacokinetic (PK) studies in paediatric patients are becoming less invasive. This will be evaluated by analysing the number of samples and volume of blood collected for each study within four different decades. METHODS A systematic literature review was performed to identify PK papers describing number of samples and volume of blood collected in studies of chi...

CONTEXT The Medical Council of India urges doctors to prescribe generic drugs as far as possible. The Indian Medical Association had responded earlier saying that it requires guarantees on the quality of generic forms of drugs. Although no published scientific reports are available on the issue of therapeutic inequivalence, unconfirmed clinician accounts and newspaper reports of therapeutic ine...

INTRODUCTION Identifying evidence-based dosing strategies is a key part of new drug development in pediatric populations. Pharmacokinetic (PK) studies can provide important information regarding how best to dose medications in children and adolescents. Utilizing scientifically supported dosing strategies provides the best chance for any given drug to demonstrate both efficacy and acceptable tol...

Introduction Pharmacokinetic (PK) of drugs in critically ill patients could vary from the general population. The pharmacokinetics of linezolid presents a high variability. Patients undergoing renal replacement therapy (RRT) could present lower linezolid concentration than expected. The pharmacokinetic/pharmacodynamic analysis (PK/ PD) is a useful tool to optimize dosing regimens of antibiotic ...

We looked for associations between pharmacokinetic (Pk) and pharmacodynamic (Pd) parameters of ciprofloxacin (CPFX) and sparfloxacin (SPFX) and the in vivo efficacy of these antimicrobials in an immunocompetent mouse model of severe Streptococcus pneumoniae pneumonia. Bacterial killing curves recorded in the lungs during the 24 h after single subcutaneous injections of the fluoroquinolones (FQs...

BACKGROUND ONO-5334 is a cathepsin K inhibitor that induced bone mineral density (BMD) gain in a phase II study in postmenopausal osteoporosis patients. Even though the antiresorptive effect could only be monitored in the morning during the study, simulation can allow the antiresorptive effect to be assessed over 24 h, with assessment of the relationship to BMD gain. METHODS Inhibition of the...

The use of urinary and/or biliary excretion data was considered as an alternative approach if the bioanalytical method lacked the appropriate sensitivity to adequately characterize the serum or plasma concentration-time profile. This approach is used for the analysis of plasma concentration-time profile under the lower limit of quantification (LLOQ) of various analytical instruments. The object...

A systems model was developed to describe the metabolism and disposition of ursodeoxycholic acid (UDCA) and its conjugates in healthy subjects based on pharmacokinetic (PK) data from published studies in order to study the distribution of oral UDCA and potential interactions influencing therapeutic effects upon interruption of its enterohepatic recirculation. The base model was empirically adap...

This study aimed to determine the influence of proton pump inhibitors (PPIs) on the pharmacokinetics of voriconazole and to characterise potential drug-drug interactions (DDIs) between voriconazole and various PPIs (omeprazole, esomeprazole, lansoprazole and rabeprazole). Using adjusted physicochemical data and the pharmacokinetic (PK) parameters of voriconazole and PPIs, physiologically based ...