Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Feb 2012
Plasma noradrenaline and state anxiety levels predict placebo response in learned immunosuppression.
Large interindividual differences exist in the presence and extent of placebo responses in both experimental and clinical studies, but little is known about possible predictors of these responses. We employed a behaviorally conditioned immunosuppression paradigm in healthy men to analyze predictors of learned placebo responses. During acquisition, the subjects received either the immunosuppressant cyclosporin A (n = 32) or a placebo (n = 14) (unconditioned stimuli (US)) together with a novel-tasting drink (conditioned stimulus (CS)). ⋯ Nonresponders (n = 17) did not show responses different from those of the controls. Multiple-regression analyses showed that baseline IL-2, plasma noradrenaline, and state anxiety predicted nearly 60% of the variance in the conditioned IL-2 response. These data provide first evidence for putative biological and psychological predictors of learned placebo responses.
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Clin. Pharmacol. Ther. · Feb 2012
Rational opioid dosing in the elderly: dose and dosing interval when initiating opioid therapy.
Opioids are the mainstay of treatment for moderate to severe pain. However, opioid therapy in the elderly is often associated with significant morbidity because of excessive ventilatory depression. The large amount of interindividual variability in opioid dose-response relationships makes it difficult to individualize the dose and dosing interval to provide safe and effective analgesia. By examining how aging affects the pharmacokinetics (PK) and pharmacodynamics (PD) of opioids, it is possible to provide a rational basis for age adjustment in opioid dosing.
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Clin. Pharmacol. Ther. · Jan 2012
ReviewBelimumab: a BLyS-specific inhibitor for the treatment of systemic lupus erythematosus.
Belimumab (Benlysta), which recently received marketing approval, is the first of a new class of immunomodulators with a novel mechanism of action. It is a specific inhibitor of the soluble B-lymphocyte stimulator (BLyS) cytokine, which has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Two large phase III randomized controlled clinical trials evaluated the safety and efficacy of belimumab combined with standard therapy and showed that the efficacy of this treatment was significantly superior to placebo plus standard therapy. Belimumab is an evidence-based therapeutic option for patients with general lupus disease activity and may signal a shift in the existing treatment paradigm from therapeutic selection targeting specific organ involvement to an approach directed at tackling multisystem disease activity and preventing the disease from worsening.
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Clin. Pharmacol. Ther. · Jan 2012
ReviewDevelopment and clinical utility of abiraterone acetate as an androgen synthesis inhibitor.
In April 2011, abiraterone acetate (AA) was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic castration-resistant prostate cancer (CRPC) after chemotherapy. The development of AA is the direct result of our increased understanding of the intricacies of the androgen receptor (AR) pathway and its natural evolution in prostate cancer cells over the course of treatment. In this paper we review the biology of the AR and how it led to the rational design of AA. We also examine the clinical development of AA, its current use, and questions to be addressed for future development.