Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jul 2008
Comparative StudyExposure-response analysis for spontaneously reported dizziness in pregabalin-treated patient with generalized anxiety disorder.
To describe the pregabalin exposure-adverse event (AE) (dizziness) relationship in patients with generalized anxiety disorder, separate models were developed for the incidence of AE and for the conditional severity of AE, given that an AE has occurred using patient data from six clinical studies. The incidence component was modeled using a nonlinear logistic regression model. ⋯ The proportional odds model including a time course of appearance and disappearance of AE could adequately describe the time course of probability of dizziness. Incorporating a transition model including Markov elements improved the model fit and greatly improved the predictability of the time course of probability of dizziness.
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The mechanism of the analgesic action of acetaminophen involves the serotonergic system. This study explores how acetaminophen interferes with serotonergic descending pain pathways. Eighteen rapid metabolizers of tropisetron were included in this double-blind cross-over study. ⋯ After CPT, AUC (%*min) of Ap (1,561+/-429) was larger than before CPT (393+/-382, P<0.05); these effects were totally inhibited by tropisetron. Acetaminophen reinforces descending inhibitory pain pathways; it suggests a supraspinal target for acetaminophen's antinociceptive action. This study also confirmed that there is a central serotonergic mechanism of action for acetaminophen that is not stimulus-dependent.