Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2018
Pan-Canadian Pharmaceutical Alliance (pCPA): Timelines Analysis and Policy Implications.
This analysis follows our recent study showing that Canadian public reimbursement delays have lengthened from regulatory approval to listing decisions by public drug plans and delayed public access to innovative medicines, mainly due to processes following the Common Drug Review (CDR) and the pan-Canadian Oncology Drug Review (pCODR). Public drug plans participate in a pan-Canadian Pharmaceutical Alliance (pCPA) joint negotiation process before making decisions about whether or not to reimburse a product reviewed through CDR and pCODR. This research aims to report the findings from a comprehensive analysis of pCPA process times, times to reimbursement by public payers in Canada, and to explore the opportunities to reduce total delays in public reimbursement with a specific focus on the pCPA process. ⋯ Listing rates also appear to be declining for non-oncology products, although this trend is less conclusive for oncology products. Challenges need to be addressed to improve efficiency, transparency, and ultimately reduce pCPA timelines and total timelines to public reimbursement. Suggested ways to improve and streamline the listing process are: (1) transparent target timelines and associated performance incentives for the pCPA and public plan decisions, (2) parallel HTA-pCPA processes to enable pCPA negotiations to start part-way through the HTA review and allow pCPA negotiation information to be fed back into the HTA review, and (3) innovative agreements that consider patient input and earlier coverage with real-world evidence development.
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Frontiers in pharmacology · Jan 2018
Sulodexide for Secondary Prevention of Recurrent Venous Thromboembolism: A Systematic Review and Meta-Analysis.
Background: Patients with venous thromboembolism have high risk of recurrence after discontinuation of anticoagulant treatment. Extended anticoagulation, such as traditional anticoagulants, can reduce the risk of recurrence but is associated with increased risk of hemorrhage. Sulodexide is a natural glycosaminoglycan mixture which can prevent recurrent venous thromboembolism. ⋯ The safety of sulodexide was also reliable. The rate of bleeding was 0.28% in the sulodexide group and 1.60% in the control group, and design of study did not influence these results. Conclusions: Sulodexide could significantly reduce the recurrence of VTE after discontinuation of anticoagulation treatment as compared with placebo.
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Frontiers in pharmacology · Jan 2018
In vitro and in vivo Pharmacological Activities of 14-O-Phenylpropyloxymorphone, a Potent Mixed Mu/Delta/Kappa-Opioid Receptor Agonist With Reduced Constipation in Mice.
Pain, particularly chronic pain, is still an unsolved medical condition. Central goals in pain control are to provide analgesia of adequate efficacy and to reduce complications associated with the currently available drugs. Opioids are the mainstay for the treatment of moderate to severe pain. ⋯ POMO-induced antinociception is mediated through the activation of the mu-opioid receptor, and it does not involve delta- and kappa-opioid receptors. In the charcoal test, POMO produced fourfold less inhibition of the gastrointestinal transit than 14-OMO and morphine. In summary, POMO emerges as a new potent mixed mu/delta/kappa-opioid receptor agonist with reduced liability to cause constipation at antinociceptive doses.
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Frontiers in pharmacology · Jan 2018
Galenic Preparations of Therapeutic Cannabis sativa Differ in Cannabinoids Concentration: A Quantitative Analysis of Variability and Possible Clinical Implications.
Introduction: Magistral preparations of therapeutic cannabis are extracted from standardized products imported from Holland or from the Florence Military Pharmaceutical Chemical Works, but extraction protocols differ among galenic laboratories. This study assessed the inter-laboratory variability in concentrations of cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabinol (THC), and tetrahydrocannabinolic acid (THCA) among different magistral oil preparations. Methods: 219 samples of Bediol, Bedrobinol, Bedrolite or FM-2 70 or 100 mg/ml in oil were collected from 3 laboratories. ⋯ As for FM-2, a significant inter-laboratories variability was found for CBD concentrations. Conclusion: Quantitative variability of cannabinoids in magistral preparations might impact on the efficacy and safety of therapeutic cannabis. A standardized protocol is needed to guarantee a homogeneous product and patients' therapeutic continuity.
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Frontiers in pharmacology · Jan 2018
ReviewRevisiting the Role of Thiopurines in Inflammatory Bowel Disease Through Pharmacogenomics and Use of Novel Methods for Therapeutic Drug Monitoring.
Azathioprine and 6-mercaptopurine, often referred to as thiopurine compounds, are commonly used in the management of inflammatory bowel disease. However, patients receiving these drugs are prone to developing adverse drug reactions or therapeutic resistance. Achieving predefined levels of two major thiopurine metabolites, 6-thioguanine nucleotides and 6-methylmercaptopurine, is a long-standing clinical practice in ensuring therapeutic efficacy; however, their correlation with treatment response is sometimes unclear. ⋯ In this review, we explore the limitations associated with the current methods used for therapeutic monitoring of thiopurine metabolites and how the recent discovery of ethnicity-specific genetic markers can complement thiopurine metabolites measurement in formulating a strategy for more accurate prediction of thiopurine response. We also discuss the challenges in thiopurine therapy, alongside the current strategies used in patients with reduced thiopurine response. The review is concluded with suggestions for future work aiming at using a more comprehensive approach to optimize the efficacy of thiopurine compounds in inflammatory bowel disease.