Proof of pharmacology of Org 48775-0, a p38 MAP kinase inhibitor, in healthy volunteers.

Aim: To investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of the highly selective oral p38alpha/beta mitogen-activated protein (MAP) kinase inhibitor Org 48,775-0 in a first-in-human study.

Methods: In the single ascending dosing (SAD) study, an oral dose of Org 48,775-0 (0.3-600 mg) was evaluated in healthy males.

Assessment of Dermal Absorption of Aluminum from a Representative Antiperspirant Formulation Using a Al Microtracer Approach.

A clinical pharmacokinetic study was performed in 12 healthy women to evaluate systemic exposure to aluminum following topical application of a representative antiperspirant formulation under real-life use conditions. A simple roll-on formulation containing an extremely rare isotope of aluminum ( Al) chlorohydrate (ACH) was prepared to commercial specifications. A Al radio-microtracer was used to distinguish dosed aluminum from natural background, using accelerated mass spectroscopy.

The effect of food on the high clearance drug asenapine after sublingual administration to healthy male volunteers.

Purpose: To determine the effects of food on the pharmacokinetics of sublingual asenapine.

Methods: Healthy male volunteers (n=26, age 19-53 years) randomly received a single sublingual dose of asenapine 5 mg after ≥ 10 h fasting (Treatment A, reference), after a high-fat meal (Treatment B) and after ≥ 10 h fasting with a high-fat meal at 4 h post-dose (Treatment C). Blood samples were drawn over 72 h to measure asenapine plasma concentrations.

Effect of sugammadex on QT/QTc interval prolongation when combined with QTc-prolonging sevoflurane or propofol anaesthesia.

Background: We evaluated the potential for QT/corrected QT (QTc) interval prolongation after sugammadex given with propofol or sevoflurane anaesthesia.

Methods: This was a two-factorial, randomized, parallel-group study in 132 healthy subjects. Anaesthesia was maintained with sevoflurane or propofol.

Pharmacokinetic profile of nomegestrol acetate and 17β-estradiol after multiple and single dosing in healthy women.

Background: The pharmacokinetics of the monophasic oral contraceptive nomegestrol acetate (NOMAC) plus 17β-estradiol (E(2)) were investigated after a single dose and multiple dosing.

Study Design: NOMAC/E2 (2.5 mg/1.

Flucloxacillin and diclofenac do not cause recurrence of neuromuscular blockade after reversal with sugammadex.

Background: Sugammadex, a modified γ-cyclodextrin, facilitates rapid reversal of rocuronium- and vecuronium-induced neuromuscular blockade (NMB). Cyclodextrins are known for their ability to form inclusion complexes with various drugs. Theoretically, molecules with a high affinity for sugammadex could interact and displace sugammadex from the sugammadex-rocuronium or sugammadex-vecuronium complex, potentially resulting in the recurrence of NMB due to recirculation of free rocuronium or vecuronium.

Valproate reduces the glucuronidation of asenapine without affecting asenapine plasma concentrations.

Asenapine is indicated for treatment of schizophrenia in the United States and acute treatment of manic or mixed episodes, as monotherapy (United States and European Union) or adjunct therapy (United States only), associated with bipolar I disorder. It is extensively metabolized; the 2 main metabolites are asenapine N-glucuronide and N-desmethyl-asenapine. The authors investigated the pharmacokinetic interactions between asenapine and valproate in an open-label, randomized, 2-way crossover study.

Safety, tolerability and pharmacokinetics of sugammadex using single high doses (up to 96 mg/kg) in healthy adult subjects: a randomized, double-blind, crossover, placebo-controlled, single-centre study.

Background And Objective: Sugammadex facilitates rapid reversal of rocuronium- and vecuronium-induced neuromuscular blockade. This study aimed to evaluate the safety, tolerability and pharmacokinetics of high doses of sugammadex (up to 96 mg/kg) in healthy subjects.

Methods: In this randomized, double-blind, crossover, placebo-controlled, single-centre study, 13 healthy adults were scheduled to receive three single intravenous doses of sugammadex in ascending order (32, 64 and 96 mg/kg) and placebo (interspersed between sugammadex doses), each separated by a 1-week washout period.