Effective inhibitors of invasion and metastasis represent a serious unmet clinical need. We have recently identified 4-fluoro-3',4',5'-trimethoxychalcone or C16 as a potent anti-invasive molecule. In this paper, we report on the development of an optimized vehicle for oral administration of C16. We also explore its pharmacokinetic and toxicity profile in rodents as a prelude to a broad-scope ev...

Oral anticoagulation therapy with warfarin is the mainstay of prevention and treatment of thromboembolic disease. However, it remains one of the leading causes of harmful medication errors and medication-related adverse events. The beneficial outcomes of oral anticoagulation therapy are directly dependent upon the quality of dose and anticoagulation management, but the literature is not robust ...

Theophylline clearance was studied in normal healthy volunteers before and after chronic oral dosing. Oral theophylline clearance showed a significant decrease (P less than 0.001) from 59.3 +/- 6.48 ml/min (mean +/- s.e. mean, n = 10) to 48.0 +/- 6.4 ml/min. Steady-state intravenous clearance decreased by 26 +/- 2% from 55.1 +/- 7.7 ml/min to 41.0 +/- 5.96 ml/min (mean +/- s.e. mean, n = 6; P l...

BACKGROUND The British National Formulary for Children (BNFC) recommends dosing oral penicillins according to age-bands, weight-bands, or weight-based calculations. Because of the rising prevalence of childhood obesity, age-band-based prescribing could lead to subtherapeutic dosing. AIM To investigate actual oral penicillin prescribing by GPs in the UK with reference to the current BNFC age-b...

There is no personalized anticancer treatment without individualized dosing. Clearly, BSA-based chemotherapy dosing does not improve the substantial pharmacokinetic variability of individual drugs. Similarly, the new oral kinase inhibitors and endocrine compounds exhibit a marked pharmacokinetic variability due to variable absorption, hepatic metabolism and potential drug-drug and food-drug int...

The pharmacokinetics of tamsulosin hydrochloride, a selective alpha1-adrenoceptor antagonist, was investigated after single iv and oral dosing to rats and dogs, and oral dosing to healthy male volunteers. After iv dosing, plasma tamsulosin concentrations declined in an apparent biexponential manner with terminal half-lives of 0.32 hr in rats and 1.13 hr in dogs. Values for total blood clearance...

PURPOSE This dose-escalation study evaluated the safety, tolerability, and pharmacokinetics (PK) of the oral Src inhibitor saracatinib (AZD0530) in patients with advanced solid malignancies. Tumor biopsy samples were taken to investigate the effect of saracatinib on Src activity in tumors. EXPERIMENTAL DESIGN Part A of the study followed a multiple-ascending dose design to establish the maxim...

List of abbreviations . . . . . . . . . . . . . . . . . . 2 Preamble: purposes and scope of the task force . . 2 Blood coagulation . . . . . . . . . . . . . . . . . . . . 3 Haemostasis . . . . . . . . . . . . . . . . . . . . . 3 Arterial thrombosis . . . . . . . . . . . . . . . . . 3 Tissue factor . . . . . . . . . . . . . . . . . . . . . 3 Tissue factor pathway inhibitor . . . . . . . . . . 3 ...

Voriconazole pharmacokinetics are not well characterized in children despite prior studies. To assess the appropriate pediatric dosing, a study was conducted in 40 immunocompromised children aged 2 to <12 years to evaluate the pharmacokinetics and safety of voriconazole following intravenous (IV)-to-oral (PO) switch regimens based on a previous population pharmacokinetic modeling: 7 mg/kg IV ev...

PURPOSE Inhibition of vascular endothelial growth factor (VEGF) signaling has shown great promise for the treatment of ocular neovascular disease. Current anti-VEGF therapies in late-stage development, while efficacious, require dosing by frequent intravitreal injections that are inconvenient to patients. VEGF signaling inhibitors that demonstrate more convenient dosing regimens could lead to t...