Postgraduate medicine
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Postgraduate medicine · Jan 2012
Randomized Controlled TrialThe pharmacokinetic parameters of a single dose of a novel nano-formulated, lower-dose oral diclofenac.
There is a clinical need for new nonsteroidal anti-inflammatory drugs (NSAIDs) and/or new formulations that, at minimum, retain the established efficacy of standard NSAIDs while minimizing their associated adverse events. This phase 1 clinical trial characterizes the pharmacokinetic (PK) profile of an investigational, proprietary, nano-formulated, lower-dose oral diclofenac (nano-formulated diclofenac) compared with oral diclofenac in healthy subjects. ⋯ The novel nano-formulated, lower-dose diclofenac demonstrated lower systemic exposure, comparable Cmax, and faster absorption compared with diclofenac. In light of the advisory issued by worldwide regulatory agencies regarding use of lowest effective doses, these data may permit use of lower NSAID doses that improve safety and tolerability while, at minimum, relieving pain similar to standard formulations.
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Postgraduate medicine · Jul 2011
Randomized Controlled TrialClinical outcomes during opioid titration following initiation with or conversion to Remoxy®, an extended-release formulation of oxycodone.
Intra- and interpatient variability in opioid response usually necessitates opioid therapy titration to optimally balance analgesia and side effects, whether initiating therapy or converting from another opioid. Remoxy® (King Pharmaceuticals, Inc., Bristol, TN, which was acquired by Pfizer Inc in March 2011) is an extended-release formulation of oxycodone designed to maintain its rate-controlling mechanism following physical and chemical manipulation. A recent phase 3 trial, which required dose titration following initiation or conversion to Remoxy, demonstrated the long-term safety and efficacy of Remoxy in relieving moderate to severe chronic pain. ⋯ Of opioid-naïve patients, 300 (76%) reached a stable dose of Remoxy (mean, 2.2 titration steps), 253 (84%) of whom successfully initiated on Remoxy. Pain intensity decreased from baseline to study completion by approximately 35% for both opioid-experienced and opioid-naïve patients and adverse events were similar to those typically reported for opioids, with a higher incidence rate reported during titration (pre-stable dose period). These data provide important clinical information when initiating opioid-naïve patients on or converting opioid-experienced patients to Remoxy.
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Postgraduate medicine · Nov 2010
Randomized Controlled Trial Comparative StudyOvercoming qEEG abnormalities and reward gene deficits during protracted abstinence in male psychostimulant and polydrug abusers utilizing putative dopamine D₂ agonist therapy: part 2.
It is well established that in both food- and drug-addicted individuals there is "dopamine resistance" associated with the DRD2 gene A1 allele. Based on earlier studies, evidence is emerging wherein the potential of utilizing a natural, nonaddicting, safe, putative D2 agonist may play a significant role in the recovery of individuals with reward deficiency syndrome, including those addicted to psychoactive chemicals. ⋯ This seminal work will provide important information that may ultimately lead to significant improvement in the recovery of individuals with psychostimulant and polydrug abuse problems, specifically those with genetically induced dopamine deficiency. Based on this small sample size, we are proposing that with necessary large populations supporting these initial results, and possibly even additional candidate genes and single nucleotide polymorphisms, we may eventually have the clinical ability to classify severity according to genotype and possession of risk alleles, along with offering a safe, nonaddicting, natural dopaminergic receptor agonist that potentially upregulates instead of downregulates dopaminergic receptors, preferably the D2 subtype.
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Postgraduate medicine · Jul 2010
Randomized Controlled Trial Multicenter StudyMorphine sulfate and naltrexone hydrochloride extended release capsules in patients with chronic osteoarthritis pain.
To assess the efficacy and safety of morphine sulfate and naltrexone hydrochloride extended release capsules (EMBEDA; MS-sNT), which contain morphine sulfate pellets with a sequestered naltrexone core, in treating patients with chronic, moderate-to-severe osteoarthritis (hip or knee) pain. ⋯ MS-sNT provided effective analgesia in patients with chronic, moderate-to-severe osteoarthritis pain, with a safety profile typical of morphine-containing products. Naltrexone sequestered in MS-sNT had no clinically relevant effect when MS-sNT was taken as directed.
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Postgraduate medicine · May 2010
Randomized Controlled TrialA systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes.
The objective was to assess the relative risk (RR) for cardiovascular (CV) events across all 8 randomized phase 2/3 trials evaluating saxagliptin in patients with type 2 diabetes mellitus. ⋯ No increased risk of CV death/MI/stroke was observed in patients randomly assigned saxagliptin across a broad drug development program. Although this systematic overview has inherent and important limitations, the data support a potential reduction in CV events with saxagliptin. The hypothesis of CV protection with saxagliptin will be tested prospectively in a large randomized clinical outcome trial evaluating saxagliptin compared with standard of care in patients with type 2 diabetes at increased risk for CV events.