British journal of clinical pharmacology
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Br J Clin Pharmacol · Mar 2015
Randomized Controlled TrialMetabolic activation and analgesic effect of flupirtine in healthy subjects, influence of the polymorphic NAT2, UGT1A1 and GSTP1.
The rare association of flupirtine with liver injury is most likely caused by reactive quinone diimines and their oxidative formation may be influenced by the activities of N-acetyltransferases (NAT) that conjugate the less toxic metabolite D13223, and by glucuronosyltransferases (UGT) and glutathione S-transferases (GST) that generate stable terminal glucuronides and mercapturic acid derivatives, respectively. The influence of genetic polymorphisms of NAT2, UGT1A1 and GSTP1 on generation of the terminal mercapturic acid derivatives and analgesic effects was evaluated to identify potential genetic risk factors for hepatotoxicity of flupirtine. ⋯ Formation of mercapturic acid derivatives is a major elimination route for flupirtine in man. However, the theoretically toxic pathway is not influenced by the frequent polymorphisms of UGT1A1, NAT2 and GSTP1.
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Br J Clin Pharmacol · Nov 2014
Randomized Controlled TrialEffects of 20 mg oral Δ(9) -tetrahydrocannabinol on the olfactory function of healthy volunteers.
Olfactory loss impairs the patient's quality of life. In individualized therapies, olfactory drug effects gain clinical importance. Molecular evidence suggests that among drugs with potential olfactory effects is Δ(9) -tetrahydrocannabinol (THC), which is approved for several indications, including neuropathic pain or analgesia in cancer patients. The present study aimed at assessing the olfactory effects of THC to be expected during analgesic treatment. ⋯ Considering the resurgence of THC in medical use for several pathological conditions, the present results indicate that THC-based analgesics may be accompanied by subjectively noticeable reductions in olfactory acuity. In particular, for patients relying on their sense of smell, this might be relevant information for personalized therapy strategies.
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Br J Clin Pharmacol · Oct 2014
Randomized Controlled TrialEvaluation of the effect of naproxen on the pharmacokinetics and pharmacodynamics of apixaban.
To assess pharmacokinetic and pharmacodynamic interactions between naproxen (a non-steroidal anti-inflammatory drug) and apixaban (an oral, selective, direct factor-Xa inhibitor). ⋯ Co-administration of naproxen with apixaban results in higher apixaban exposure and appears to occur through increased apixaban bioavailability. The effects on anti-Xa activity, INR and inhibition of AAI-PA observed in this study were consistent with the individual pharmacologic effects of apixaban and naproxen.
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Br J Clin Pharmacol · Jul 2014
Randomized Controlled Trial Multicenter StudyA phase II, randomized, placebo-controlled, double-blind, multi-dose study of SRT2104, a SIRT1 activator, in subjects with type 2 diabetes.
SRT2104 is a selective activator of SIRT1. In animal models, SRT2104 improves glucose homeostasis and increases insulin sensitivity. We evaluated the tolerability and pharmacokinetics of SRT2104, and its effects on glycaemic control, in adults with type 2 diabetes mellitus. ⋯ Treatment with SRT2104 for 28 days did not result in improved glucose or insulin control which is likely due to the observed pharmacokinetics which were not dose proportional and had large between subject variability.