British journal of clinical pharmacology
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Br J Clin Pharmacol · Sep 2011
Population pharmacokinetic-pharmacodynamic analysis for sugammadex-mediated reversal of rocuronium-induced neuromuscular blockade.
An integrated population pharmacokinetic-pharmacodynamic model was developed with the following aims: to simultaneously describe pharmacokinetic behaviour of sugammadex and rocuronium; to establish the pharmacokinetic-pharmacodynamic model for rocuronium-induced neuromuscular blockade and reversal by sugammadex; to evaluate covariate effects; and to explore, by simulation, typical covariate effects on reversal time. ⋯ Simulations of the therapeutic dosing regimens demonstrated limited impact of age, renal function and sevoflurane use, as predicted reversal time in typical subjects was always <2 min.
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To assess the level of paracetamol off label prescribing in the community and the potential for paracetamol under or overdosing. ⋯ Paracetamol off label prescribing is common in primary care, with relatively high levels of potential overdosing in the youngest children and potential underdosing in the oldest children.
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The hypertensive disorders of pregnancy (HDP) are a leading cause of maternal mortality and morbidity in both well and under-resourced settings. Maternal, fetal, and neonatal complications of the HDP are concentrated among, but not limited to, women with pre-eclampsia. Pre-eclampsia is a systemic disorder of endothelial cell dysfunction and as such, blood pressure (BP) treatment is but one aspect of its management. ⋯ Although antihypertensive therapy may decrease the occurrence of BP values of 160-170/100-110 mmHg, therapy may also impair fetal growth. The potential benefits and risks do not seem to be associated with any particular drug or drug class. Oral labetalol and methyldopa are used most commonly, but many different β-adrenoceptor blockers and calcium channel blockers have been studied in clinical trials.
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Br J Clin Pharmacol · Aug 2011
Randomized Controlled TrialSB-656933, a novel CXCR2 selective antagonist, inhibits ex vivo neutrophil activation and ozone-induced airway inflammation in humans.
Receptor antagonists that block the binding of chemokines such as CXCL8 (IL-8) are effective in animals models of neutrophil-mediated inflammation. It has been hypothesized that selective inhibition of neutrophil trafficking and activation may be a useful adjunct for the treatment of inflammatory airway diseases such as chronic obstructive pulmonary disease or cystic fibrosis. A CXCR1/2 receptor antagonist has shown activity in an ozone challenge model in humans. ⋯ SB-656933 is a CXCR2 antagonist that demonstrates dose-dependent effects on neutrophil activation and recruitment within a well-tolerated dose range. These data suggest that SB-656933 may be an effective agent in neutrophil-predominant diseases.
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Br J Clin Pharmacol · Aug 2011
Randomized Controlled TrialPharmacokinetics, pharmacodynamics and safety of a human anti-IL-6 monoclonal antibody (sirukumab) in healthy subjects in a first-in-human study.
Interleukin (IL)-6 is a cytokine known for pleiotropic and pro-inflammatory functions. IL-6 is involved in various disease processes including lupus erythematosus, rheumatoid arthritis, insulin resistance and malignancy. Anti-IL-6 receptor therapy has recently been demonstrated to be effective in the treatment of patients with rheumatoid arthritis. ⋯ Sirukumab had a well-tolerated safety profile, desirable PK characteristics and a low incidence of immunogenicity following an i.v. infusion of 0.3 to 10 mg kg(-1) in healthy subjects.