Clinical drug investigation
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A combination of the atypical antipsychotic olanzapine and opioid receptor antagonist samidorphan (OLZ/SAM) is in development for the treatment of schizophrenia. The goal of OLZ/SAM is to provide the antipsychotic efficacy of olanzapine while mitigating olanzapine-induced weight gain and many associated long-term metabolic consequences. The primary metabolic pathways for olanzapine are direct glucuronidation via uridine 5'-diphospho-glucuronosyltransferase (UGT)1A4 and cytochrome P450 (CYP)-mediated oxidation, mainly by CYP1A2. In contrast, the samidorphan metabolic pathway is mediated predominantly by CYP3A4. ⋯ Coadministration with rifampin decreased total systemic exposure (based on AUC∞) of olanzapine and samidorphan by 48% and 73%, respectively.
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Suvorexant is an orexin receptor antagonist indicated for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance. As suvorexant is metabolized primarily by Cytochrome P450 3A (CYP3A), and its pharmacokinetics may be affected by CYP3A modulators, the effects of CYP3A inhibitors (ketoconazole or diltiazem) or an inducer (rifampin [rifampicin]) on the pharmacokinetics, safety, and tolerability of suvorexant were investigated. ⋯ These results are consistent with expectations that strong CYP3A inhibitors and inducers exert marked effects on suvorexant pharmacokinetics. In the context of a limited sample size, single suvorexant doses were generally well tolerated in healthy subjects when co-administered with/without a CYP3A inhibitor/inducer.
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The sufentanil 30 μg sublingual tablet (hereafter referred to as the sufentanil ST) is approved in the EU for acute moderate to severe pain in adults (Dzuveo™) and in the USA for acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate (Dsuvia™). It is a single-strength tablet housed in a single-dose applicator (which may minimize the likelihood of dosing errors) and is strictly for use in medically supervised/monitored settings. It is administered by a healthcare professional and has a minimum re-dose interval of 1 h and no drug delivery setup requirements. ⋯ Such short-term use of the sufentanil ST was also generally well tolerated. Studies directly comparing the sufentanil ST with other opioids in terms of efficacy, tolerability, usability and cost effectiveness would be beneficial, as would analyses of its abuse potential, given sufentanil is considerably more potent than fentanyl or morphine. In the meantime, current data indicate that the sufentanil ST is a noninvasive, fast-acting, opioid formulation for managing moderate to severe acute pain in medically supervised/monitored settings that may be of particular use when oral or intravenous opioid analgesia is not possible/feasible.
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Adverse cutaneous drug reactions associated with antiepileptic drugs (AEDs) are a serious problem in the clinical setting. New-generation AEDs have been reported to be better tolerated than old-generation forms; however, information about the risks of adverse cutaneous drug reactions to new-generation AEDs is limited. ⋯ There are clear differences in the risk of cutaneous reactions among AEDs, and further studies are needed to confirm these findings.
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Phenylketonuria is a well-known rare disease included in the neonatal screening of many countries. Therefore, there are few published data on the admissions and costs of phenylketonuria in Spain. ⋯ The access to economic and social data on phenylketonuria in Spain has been updated. The number of admissions in Spain between 1997 and 2015 and healthcare costs between 1999 and 2015 were calculated. There were 24 admissions as a result of a phenylketonuria diagnosis in 2015 and the mean healthcare cost per patient was €4239.32. This information can help to adapt and improve each healthcare system to take into consideration rare diseases.