British journal of clinical pharmacology
-
Br J Clin Pharmacol · Oct 2017
Randomized Controlled TrialAssessment of effect of CYP3A inhibition, CYP induction, OATP1B inhibition, and high-fat meal on pharmacokinetics of the JAK1 inhibitor upadacitinib.
Upadacitinib (ABT-494) is a selective Janus kinase 1 inhibitor being developed for treatment of auto-immune inflammatory disorders. This work evaluated effects of high-fat meal, cytochrome P450 (CYP) 3A inhibition, CYP induction, and organic anion transporting polypeptide (OATP) 1B inhibition on upadacitinib pharmacokinetics. ⋯ Strong CYP3A inhibition and broad CYP induction result in a weak and moderate effect, respectively, on upadacitinib exposures. OATP1B inhibition and administration of upadacitinib immediate-release formulation with food does not impact upadacitinib exposure.
-
Br J Clin Pharmacol · Jul 2017
Randomized Controlled TrialRemote ischaemic preconditioning suppresses endogenous plasma nitrite during ischaemia-reperfusion: a randomized controlled crossover pilot study.
The aim of this article is to test the hypothesis that remote ischaemic preconditioning (RIPC) increases circulating endogenous local and systemic plasma (nitrite) during RIPC and ischaemia-reperfusion (IR) as a potential protective mechanism against ischaemia-reperfusion injury (IRI). ⋯ RIPC had no effect on plasma (nitrite) during the RIPC sequence, but instead decreased plasma (nitrite) by ~25% during IR. This would likely counteract the protective mechanisms of RIPC, and contribute to RIPC's lack of efficacy, as observed in recent clinical trials. A combined approach of RIPC with nitrite administration may be required.
-
Br J Clin Pharmacol · May 2017
Randomized Controlled TrialFirst-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis.
To assess safety, pharmacokinetics (PK) and clinical efficacy of bimekizumab (formerly UCB4940), a novel humanized monoclonal antibody and dual inhibitor of interleukin (IL)-17A and IL-17F, in subjects with mild plaque psoriasis. ⋯ This is the first study to demonstrate the safety, tolerability and clinical efficacy of a dual IL-17A and IL-17F inhibitor, in subjects with mild psoriasis. Bimekizumab showed fast onset of clinically-meaningful efficacy by Week 2, with a maximal or near-maximal magnitude of response that was maintained up to study Weeks 12-20. These findings support the continued clinical development of bimekizumab for diseases mediated by both IL-17A and IL-17F, including psoriasis.
-
Br J Clin Pharmacol · Apr 2017
Randomized Controlled Trial Multicenter StudyRandomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection.
No randomized study has been conducted to investigate the use of intravenous paracetamol (acetaminophen, APAP) for the management of fever due to infection. The present study evaluated a new ready-made infusion of paracetamol. ⋯ The 1 g paracetamol formulation has a rapid and sustainable antipyretic effect on fever due to infection. Its efficacy is dependent on hepatic metabolism.
-
Br J Clin Pharmacol · Apr 2017
Randomized Controlled Trial Comparative StudyVenlafaxine and oxycodone have different effects on spinal and supraspinal activity in man: a somatosensory evoked potential study.
Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat severe and moderate pain, but their mechanisms of action in humans remain unclear. The present study aimed to explore how oxycodone (an opioid) and venlafaxine (an SNRI) modulate spinal and supraspinal sensory processing. ⋯ Opioids and SNRI drugs exert different central effects. The present study contributed to the much-needed human models of the mechanisms of action of drugs with effects on the central nervous system.