Pharmacokinetics and pharmacodynamics of argatroban in combination with a platelet glycoprotein IIB/IIIA receptor antagonist in patients undergoing percutaneous coronary intervention.

The pharmacokinetic-pharmacodynamic (PK-PD) relationship of argatroban, administered in combination with a platelet glycoprotein IIb/IIIa receptor antagonist, was characterized in patients undergoing percutaneous coronary intervention (PCI). Plasma argatroban and activated clotting times (ACTs) were assessed periprocedurally in 152 patients administered argatroban (250- or 300-microg/kg bolus, then 15-microg/kg/min infusion) in combination with abciximab or eptifibatide during PCI. The PK and PK-PD models were developed utilizing a sequential population approach in NONMEM.

Metabolism of [14C]trichloroethylene to 14CO2 and interaction of a metabolite with liver DNA in rats and mice.

Male Sprague-Dawley rats and male B6C3F1 mice excreted 5-15% of a tracer dose of [14C]trichloroethylene as 14CO2 within 24 h after ip injection of a single dose in a corn-oil vehicle. The proportion of the dose excreted as CO2 was greater in mice than in rats, but increased in the rats after starvation or pretreatment with phenobarbital. As the dose was increased toward the LD50 level, the proportion excreted as 14CO2 decreased slightly, but this was largely due to increased loss of unchanged trichloroethylene.

Activation of the rat liver glucocorticoid--receptor complex.

The rat liver glucorcorticoid receptor has been activated using three procedures: heat, gel filtration, and dilution. With time after heat activation the steroid--receptor complex loses its capacity to bind to DNA--cellulose, while receptor activated by Sephadex G-25 and by dilution maintains DNA--cellulose binding capacity. The rates of steroid dissociation from nonactivated and activated receptor and essentially identical.