Clindamycin may be active against methicillin-resistant Staphylococcus aureus, a common pathogen causing sepsis in infants, but optimal dosing in this population is unknown. We performed a multicenter, prospective pharmacokinetic (PK) and safety study of clindamycin in infants. We analyzed the data using a population PK analysis approach and included samples from two additional pediatric trials...

PURPOSE Docetaxel pharmacokinetic (PK) parameters, notably clearance and exposure (AUC), are characterized by large interindividual variability. The purpose of this study was to evaluate the effect of PK-guided [area under the plasma concentration versus time curve (AUC) targeted], individualized docetaxel dosing on interindividual variability in exposure. EXPERIMENTAL DESIGN A limited sampli...

BACKGROUND Blood-brain equilibration rate constant (ke0 ) is derived from either pharmacokinetic and pharmacodynamic modeling (k e0_model) or a model-independent observed time to peak effect (k e0_tpeak). Performance in bispectral index (BIS) prediction was compared between k e0_model and k e0_tpeak for microemulsion or long chain triglyceride (LCT) propofol. METHODS Time to peak effect (tpea...

AIM Aflibercept (VEGF-Trap), a novel anti-angiogenic agent that binds to VEGF, has been investigated for the treatment of cancer. The aim of this study was to develop a mechanism-based pharmacokinetic (PK) model for aflibercept to characterize its binding to VEGF and its PK properties in healthy subjects. METHODS Data from two phase I clinical studies with aflibercept administered as a single...

A method for assessing the extent of bioavailability (EBA) of human insulin from pharmacological data was determined. The time course governing increases in the plasma concentration of immuno-reactive insulin (IRI), as well as its pharmacological effects (glucodynamics), was determined after the intravascular administration of varying doses of human insulin. Pharmacokinetic (PK), pharmacodynami...

INTRODUCTION Chagas disease, caused by the parasite Trypanosoma cruzi, can lead to long term cardiac morbidity. Treatment of children with benznidazole is effective, but no pediatric pharmacokinetics data are available and clinical pharmacology information on the drug is scarce. PATIENTS AND METHODS Prospective population pharmacokinetic (PK) cohort study in children 2-12 years old with Chaga...

OBJECTIVE We sought to directly compare secondhand smoke (SHS) atmospheric markers to each other and to SHS dosimetric biomarkers, permitting intercomparison of clinical and atmospheric studies. METHODS We used atmospheric and pharmacokinetic (PK) models for the quantitative estimation of SHS exposure and dose for infants, children, and adults, based on building smoker density and air exchang...

Lacosamide (LCM) is an antiepileptic drug approved as adjunctive therapy for partial-onset seizures in adults. It has a mechanism of action that differs from other antiepileptic drugs in that it selectively enhances sodium channel slow inactivation, which is in contrast to 'traditional' sodium channel blockers (e.g., carbamazepine, oxcarbazepine, lamotrigine and phenytoin) that primarily affect...

Square-wave adsorptive cathodic stripping voltammetry was used to determine pioglitazone HCl in Britton Robinson buffer of pH5. The adsorptive cathodic peak was observed at -1.5 V vs. Ag/AgCl. The peak response was characterized with respect to pH, supporting electrolyte, frequency, scan increment, pulse-amplitude, accumulation potential and pre-concentration time. Under optimal conditions, the...

A preclinical drug candidate, MRK-1 (Merck candidate drug parent compound), was found to elicit tumor regression in a mouse xenograft model. Analysis of samples from these studies revealed significant levels of two circulating metabolites, whose identities were confirmed by comparison with authentic standards using liquid chromatography-tandem mass spectrometry. These metabolites were found to ...