Pharmacokinetics of dexamethasone in a rat model of rheumatoid arthritis.

Dexamethasone (DEX) is often given for the treatment of rheumatoid arthritis and clinical dosing regimens of DEX have often been based empirically. This study tests whether the inflammation processes in a rat model of rheumatoid arthritis alters the clearance and volume of distribution of DEX when compared with healthy controls. Groups of healthy and arthritic male Lewis rats received either a low (0.

Modeling corticosteroid effects in a rat model of rheumatoid arthritis I: mechanistic disease progression model for the time course of collagen-induced arthritis in Lewis rats.

A mechanism-based model was developed to describe the time course of arthritis progression in the rat. Arthritis was induced in male Lewis rats with type II porcine collagen into the base of the tail. Disease progression was monitored by paw swelling, bone mineral density (BMD), body weights, plasma corticosterone (CST) concentrations, and tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and glucocorticoid receptor (GR) mRNA expression in paw tissue.

Modeling corticosteroid effects in a rat model of rheumatoid arthritis II: mechanistic pharmacodynamic model for dexamethasone effects in Lewis rats with collagen-induced arthritis.

A mechanism-based model for pharmacodynamic effects of dexamethasone (DEX) was incorporated into our model for arthritis disease progression in the rat to aid in identification of the primary factors responsible for edema and bone loss. Collagen-induced arthritis was produced in male Lewis rats after injection of type II porcine collagen. DEX was given subcutaneously in single doses of 0.

Modeling of corticosteroid effects on hepatic low-density lipoprotein receptors and plasma lipid dynamics in rats.

Purpose: This study examines methylprednisolone (MPL) effects on the dynamics of hepatic low-density lipoprotein receptor (LDLR) mRNA and plasma lipids associated with increased risks for atherosclerosis.

Materials And Methods: Normal male Wistar rats were given 50 mg/kg MPL intramuscularly (IM) and sacrificed at various times. Measurements included plasma MPL and CST, hepatic glucocorticoid receptor (GR) mRNA, cytosolic GR density and hepatic LDLR mRNA, and plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), and triglycerides (TG).

Modeling receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase dynamics in rats: dual regulation by endogenous and exogenous corticosteroids.

Receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase (TAT) were evaluated in normal rats. A group of normal male Wistar rats were injected with 50 mg/kg methylprednisolone (MPL) intramuscularly at the nadir of their plasma corticosterone (CST) rhythm (early light cycle) and sacrificed at various time points up to 96 h post-treatment. Blood and livers were collected to measure plasma MPL, CST, hepatic glucocorticoid receptor (GR) mRNA, cytosolic GR density, TAT mRNA, and TAT activity.

Pharmacokinetics of methylprednisolone after intravenous and intramuscular administration in rats.

Methylprednisolone (MPL) pharmacokinetics was examined in adrenalectomized (ADX) and normal rats to assess the feasibility of intramuscular (i.m.) dosing for use in pharmacodynamic studies.

Physiologically based pharmacokinetic modeling of FTY720 (2-amino-2[2-(-4-octylphenyl)ethyl]propane-1,3-diol hydrochloride) in rats after oral and intravenous doses.

FTY720 (2-amino-2[2-(-4-octylphenyl)ethyl]propane-1,3-diol hydrochloride) is a new sphingosine-1-phosphate receptor agonist being developed for multiple sclerosis and prevention of solid organ transplant rejection. A physiologically based pharmacokinetic model was developed to predict the concentration of FTY720 in various organs of the body. Single oral and intravenous doses of FTY720 were administered to male Wistar rats, with blood and tissue sampling over 360 h analyzed by liquid chromatography/tandem mass spectrometry.

Modeling glucocorticoid-mediated fetal lung maturation: I. Temporal patterns of corticosteroids in rat pregnancy.

Preterm birth produces neonatal respiratory distress syndrome, and dexamethasone (DEX) is administered maternally to induce fetal lung maturation in women at risk of preterm delivery. Antenatal DEX therapy is largely empirical, and administering multiple doses of DEX produces undesirable metabolic and developmental effects in the fetus. It is hypothesized that pharmacokinetic/pharmacodynamic (PK/PD) assessment of the maternal/fetal disposition and selected effects of corticosteroids will allow insight into optimal dosing methods.

Modeling glucocorticoid-mediated fetal lung maturation: II. Temporal patterns of gene expression in fetal rat lung.

Our previous report described the temporal steroid patterns during pharmacokinetic (PK) studies with dexamethasone (DEX) where doses of six 1 micromol/kg injections were given during gestational ages 18 to 20 days in rats. DEX PK was used in conjunction with the endogenous corticosterone profile to understand the regulation of fetal lung pharmacodynamics (PD). Expression of the glucocorticoid receptor (GR) and surfactant proteins A and B mRNA were chosen as lung maturational markers.

Pharmacodynamic interactions between recombinant mouse interleukin-10 and prednisolone using a mouse endotoxemia model.

The pharmacodynamic interactions between recombinant mouse interleukin-10 (IL-10) and prednisolone were examined in lipopolysaccharide (LPS)-induced experimental endotoxemia in Balb/c mice. Treatment phases consists of single doses of IL-10 (10 microg/kg i.p.

Integrated QSPR--pharmacodynamic model of genomic effects of several corticosteroids.

The results from a quantitative structure-property relationship (QSPR) model was integrated into a fifth-generation pharmacokinetic/pharmacodynamic (PK/PD) model of corticosteroid receptor/gene-mediated effects. The proposed model was developed using previously reported tyrosine aminotransferase (TAT) activity data following a 50 mg/kg intravenous dose of methylprednisolone in male adrenalectomized (ADX) rats. Induced TAT activity is a classical measure of corticosteroid genomic effects and the typical time course shows an initial lag-time, a slow rise to peak response, and a gradual return toward baseline values.

Fifth-generation model for corticosteroid pharmacodynamics: application to steady-state receptor down-regulation and enzyme induction patterns during seven-day continuous infusion of methylprednisolone in rats.

A fifth-generation model for receptor/gene-mediated corticosteroid effects was proposed based on results from a 50 mg/kg i.v. bolus dose of methylprednisolone (MPL) in male adrenalectomized rats, and confirmed using data from other acute dosage regimens.

Pharmacodynamics and pharmacogenomics of methylprednisolone during 7-day infusions in rats.

An array of adverse steroid effects was examined on a whole body, tissue, and molecular level. Groups of male adrenalectomized Wistar rats were subcutaneously implanted with Alzet mini-pumps giving zero-order release rates of 0, 0.1, and 0.