Lyophilized Filovirus Glycoprotein Vaccines: Peroxides in a Vaccine Formulation with Polysorbate 80-Containing Adjuvant are Associated with Reduced Neutralizing Antibody Titers in Both Mice and Non-Human Primates.

Zaire ebolavirus, Sudan ebolavirus, and Marburg marburgvirus are the filoviruses most commonly associated with human disease. Previously, we administered a three-dose regimen of trivalent vaccines comprising glycoprotein antigens from each virus in mice and non-human primates (NHPs). The vaccines, which contained a polysorbate 80-stabilized squalane-in-water emulsion adjuvant and were lyophilized from a solution containing trehalose, produced high antibody levels against all three filovirus antigens.

Effect of hepatic impairment on the pharmacokinetics of atomoxetine and its metabolites.

Background And Objectives: Atomoxetine is a treatment for attention-deficit/hyperactivity disorder and is primarily eliminated via cytochrome P4502D6 (CYP2D6). The pharmacokinetics of atomoxetine and its primary metabolites were investigated in 10 adults with hepatic impairment (6 moderate, 4 severe) and 10 age- and sex-matched control subjects, all being genotyped as CYP2D6 extensive metabolizers.

Methods: A single oral 20-mg dose of atomoxetine was given.

Disposition and metabolic fate of atomoxetine hydrochloride: the role of CYP2D6 in human disposition and metabolism.

The role of the polymorphic cytochrome p450 2D6 (CYP2D6) in the pharmacokinetics of atomoxetine hydrochloride [(-)-N-methyl-gamma-(2-methylphenoxy)benzenepropanamine hydrochloride; LY139603] has been documented following both single and multiple doses of the drug. In this study, the influence of the CYP2D6 polymorphism on the overall disposition and metabolism of a 20-mg dose of (14)C-atomoxetine was evaluated in CYP2D6 extensive metabolizer (EM; n = 4) and poor metabolizer (PM; n = 3) subjects under steady-state conditions. Atomoxetine was well absorbed from the gastrointestinal tract and cleared primarily by metabolism with the preponderance of radioactivity being excreted into the urine.

Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics.

The purpose of this study was to characterize the effect of potent CYP2D6 inhibition byparoxetine on atomoxetine disposition in extensive metabolizers. This was a single-blind, two-period, sequential studyin 22 healthy individuals. In period 1, 20 mg atomoxetine bid was administered to steady state.