Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Feb 2015
Clinical TrialOndansetron pharmacokinetics in pregnant women and neonates: towards a new treatment for neonatal abstinence syndrome.
Ondansetron is the drug of choice to prevent nausea in women undergoing cesarean surgery and can be used to prevent neonatal abstinence syndrome (NAS). The pharmacokinetics of ondansetron have not been characterized in pregnant women or in newborns. ⋯ A dosing regimen for prevention of NAS was designed based on the model. The regimen involves IV administration of 4 mg to the mothers shortly before cord clamping, or oral administration of 0.07 mg/kg (or equivalently 0.04 mg/kg IV) to neonates.
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Clin. Pharmacol. Ther. · Feb 2015
ReviewNocebo vs. placebo: the challenges of trial design in analgesia research.
The placebo effect in randomized clinical trials appears to have increased thereby contributing to problems of demonstrating statistically reliable effects of treatments that directly target biological mechanisms. The shortcomings of randomized clinical trials are currently discussed along with potential improvements of trial designs. ⋯ We present three major challenges in randomized clinical trials: (i) increasing placebo effects, (ii) variability of the placebo effect, and (iii) risk of un-blinding. We then explain how recent placebo and nocebo studies of effects of verbal suggestion, expectancy, and emotions may improve understanding and discussion of increasing placebo effects, account/control for large parts of the variability of placebo effects, and suggest ways to improve blinding in future trials.
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Existing analgesics fail to provide adequate pain relief in a significant proportion of patients complaining of chronic pain. Furthermore, their use is limited by tolerability and safety concerns. Thus, there is a huge unmet need for effective and safe innovative painkillers. Considering the major role of nerve growth factor (NGF) in the generation and maintenance of a wide range of pain states, the issue is whether anti-NGF biologics under development might offer such an opportunity.
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Patients with the same disease may suffer from completely different pain symptoms yet receive the same drug treatment. Several studies elucidate neuropathic pain and treatment response in human surrogate pain models. They show promising results toward a patient stratification according to the mechanisms underlying the pain, as reflected in their symptoms. ⋯ However, retrospective analysis of treatment response based on baseline pain phenotyping could demonstrate positive results for certain subgroups of patients. Thus, a prospective classification of patients according to pain phenotype may play an increasingly important role in personalized treatment of neuropathic pain states. A recent prospective study using stratification based on pain-related sensory abnormalities confirmed the concept of personalized pharmacological treatment of neuropathic pain.
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Clin. Pharmacol. Ther. · Feb 2015
Angiotensin II type 2-receptor: new clinically validated target in the treatment of neuropathic pain.
Neuropathic pain is a large unmet medical need. The angiotensin II type 2 (AT2 ) receptor is a target with promising data in rodent models of peripheral neuropathic pain. The AT2 receptor has attracted attention on the basis of human data from a proof-of-concept clinical trial showing that oral EMA401, a highly selective, peripherally restricted, small molecule AT2 receptor antagonist, at 100 mg twice-daily for 4 weeks, alleviated postherpetic neuralgia, an often intractable type of peripheral neuropathic pain.