Physiologically based pharmacokinetic (PBPK) modeling of everolimus (RAD001) in rats involving non-linear tissue uptake.

Everolimus is a novel macrolide immunosuppressant developed for the prophylaxis of allogeneic renal or cardiac transplant rejection. Treatments with immunosuppressants are often associated with organ toxicity that is linked to high organ exposure. Therefore, gaining insight into the pharmacokinetics of everolimus in various organs is highly desirable especially those organs of therapeutic interest or those that pose safety concerns.

Preferential cerebrospinal fluid acetylcholinesterase inhibition by rivastigmine in humans.

This study sought to examine the feasibility of prolonged assessment of acetylcholinesterase (AChE) activity in the cerebrospinal fluid (CSF) of volunteers and to test the hypothesis that rivastigmine (ENA-713; Exelon, Novartis Pharma AG, Basel, Switzerland) selectively inhibits AChE in CSF in humans at a dose producing minimal inhibition of the peripheral enzyme. Lumbar CSF samples were collected continuously (0.1 mL x min(-1)) for 49 hours from eight healthy volunteers who took either placebo or a single oral dose of rivastigmine (3 mg).

Absorption, metabolism, and disposition of [14C]SDZ ENA 713, an acetylcholinesterase inhibitor, in minipigs following oral, intravenous, and dermal administration.

Purpose: SDZ ENA 713 (rivastigmine) is an acetylcholinesterase inhibitor intended for therapeutic use in Alzheimer's disease. The present study compared the pharmacokinetics of [14C]SDZ ENA 713 after intravenous, oral, and dermal administration to male minipigs, and also examined the effects of dose level and skin abrasion on transdermal absorption.

Methods: Four groups of 3 minipigs each received a single intravenous (0.

Exploratory analysis of population pharmacokinetic data from clinical trials with application to isradipine.

Drug level monitoring during routine clinical visits in the course of phase III trials provides a means to document pharmacokinetic variability in a patient population. Such a pharmacokinetic screen was performed for the new calcium antagonist isradipine. A total of 697 blood samples were collected at any time after the morning dose from 252 patients who had received oral doses of isradipine.

Pharmacokinetics of isradipine in patients with chronic liver disease.

The pharmacokinetics of the dihydropyridine calcium antagonist isradipine has been examined in 8 healthy volunteers, 7 patients with non-cirrhotic chronic liver disease (CLD), and 8 patients with biopsy-proven cirrhosis (CIR). Isradipine was simultaneously given orally (12C 5 mg) and i.v.