Pharmacokinetic-pharmacodynamic assessment of topiramate dosing regimens for children with epilepsy 2 to <10 years of age.

Purpose: To identify and validate the efficacious monotherapy dosing regimen for topiramate in children aged 2 to <10 years with newly diagnosed epilepsy using pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation bridging.

Methods: Several models were developed in pediatric and adult populations to relate steady-state trough plasma concentrations (C(min)) of topiramate to the magnitude of clinical effect in monotherapy and adjunctive settings. These models were integrated to derive and support the monotherapy dosing regimen for pediatric patients.

Sirolimus (rapamycin, Rapamune) and combination therapy with cyclosporin A in the rat developing adjuvant arthritis model: correlation with blood levels and the effects of different oral formulations.

Objective And Design: To determine whole blood levels of sirolimus, a macrolide antibiotic in the rat developing adjuvant arthritis (AA) model after dosing orally with two different vehicles, and whether combinational doses of sirolimus and cyclosporin A (CsA) produced additive or synergistic inhibitory effects in this model.

Material: Male Lewis rats (150-180g).

Treatment: Arthritis was induced by the injection (0.

The effects of antiinflammatory and antiallergic drugs on cytokine release after stimulation of human whole blood by lipopolysaccharide and zymosan A.

IL-1 beta, IL-8, IL-6 and TNF alpha, derived from infiltrating leukocytes, are important mediators of inflammation in arthritic and allergic diseases. Heparinized human whole blood was evaluated as a model to study the effects of various classes of antiinflammatory drugs on cytokine release/biosynthesis from leukocytes. Whole blood was stimulated with zymosan A (1.

The effects of anti-inflammatory and antiallergic drugs on the release of IL-1 beta and TNF-alpha in the human whole blood assay.

Heparinized human whole blood was evaluated as a model to study the effects of various classes of anti-inflammatory drugs on IL-1 beta and TNF-alpha release from leukocytes. Human whole blood was stimulated with zymosan (1.5 mg/ml) or LPS (5 micrograms/ml) to induce significant cytokine release.

Inhibition of endotoxin-induced hypothermia and serum TNF-alpha levels in CD-1 mice by various pharmacological agents.

Intraperitoneal injection of lipopolysaccharide (LPS) was used to elicit a sublethal, shock-like condition in mice. LPS, 2.5 mg/kg i.