Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Apr 2021
Remdesivir potently inhibits carboxylesterase-2 through covalent modifications: signifying strong drug-drug interactions.
Remdesivir was recently approved to treat COVID-19. While this antiviral agent delivers clinical benefits, several safety concerns in many cases have been raised. ⋯ CES2 is a major drug-metabolizing enzyme. The combination of high potency with irreversible inhibition concludes that cautions must be exercised when remdesivir is used along with drugs hydrolyzed by CES2.
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Fundam Clin Pharmacol · Feb 2021
Outcome of patients hospitalized for COVID-19 and exposure to angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in France: results of the ACE-CoV study.
Data are lacking on the impact of ACEI/ARB exposure on unfavorable outcome in the population of patients hospitalized for COVID-19 with hypertension/cardiovascular disease, particularly in Europe. The ACE-CoV study was designed to assess this question. The study was conducted in the Covid-Clinic-Toul cohort, which contains data about all patients hospitalized at Toulouse University hospital, France with a SARS-CoV-2 infection since March, 2020. ⋯ Analyses with weighting by the IPTW-PS method gave similar results. Results were similar when considering the subgroup of patients with arterial hypertension. The ACE-CoV study found no association between exposure to ACEIs or ARBs and unfavorable outcome in hospitalized patients for COVID-19 with a history of cardiovascular disease/arterial hypertension.
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Fundam Clin Pharmacol · Dec 2019
Tranexamic acid through intravenous, intramuscular and oral routes: an individual participant data meta-analysis of pharmacokinetic studies in healthy volunteers.
Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post-partum haemorrhage. One key issue for treatment success is early administration. While usually given intravenously, oral and intramuscular use would be useful in specific circumstances. ⋯ Oral and IM bioavailabilities were 46 and 105%, respectively. For a 70 kg bodyweight, the population estimates were 7.6 L/h for clearance, 17.9 L for the volume of the central compartment, 2.5 L/h for the diffusional clearance and 16.6 L for the peripheral volume of distribution. Larger well-designed studies are needed to describe the pharmacokinetics of TXA when given IM or as an oral solution before these can be recommended as alternatives to IV.
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Fundam Clin Pharmacol · Jun 2019
Randomized Controlled TrialN-acetylcysteine prevents glutathione decrease and does not interfere with paracetamol antinociceptive effect at therapeutic dosage: a randomized double-blind controlled trial in healthy subjects.
Paracetamol (APAP) may lead to hepatic changes even at therapeutic dosages. Glutathione (GSH) plays a pivotal role in APAP metabolism as it allows the detoxification of a toxic metabolite. N-Acetylcysteine (NAC) is APAP antidote, is also largely used as a mucoactive drug and is often associated with APAP. ⋯ This study shows for the first time that APAP antinociceptive effectiveness is not influenced by NAC. It also shows that the effect of APAP at therapeutic dosage on GSH may be counteracted by NAC. These issues are particularly important for patients as APAP is often prescribed for years as a first-line pain treatment and further trials in patients are now warranted.
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Fundam Clin Pharmacol · Jun 2019
Is there overuse of proton pump inhibitors in B-cell non-Hodgkin lymphomas? A cohort study based on the French health insurance database in the Midi-Pyrénées region.
Patients suffering from B-cell non-Hodgkin lymphomas (B-NHL) have an increased likelihood of being exposed to proton pump inhibitors (PPIs), related to several factors which have been reported in the literature. PPIs are among the drugs most likely to be prescribed inappropriately. Consequently, B-NHL patients could be particularly at risk of inappropriate PPI prescription, with potential adverse drug reactions. ⋯ Determinants of PPIs initiation were peptic ulcer disease, gastroprotection (appropriate or not) for medications considered at risk (NSAIDs, glucocorticoids and anticoagulants), age, nonfollicular lymphoma, polypharmacy, gastroenterologists' consultations and being hospitalized in a university hospital. Around 50% of patients initiated PPI treatment during the chemotherapy phase with only one-fifth identified as appropriate prescriptions and with long durations of treatment in most cases. Given this background, appropriate PPI prescription should be promoted in B-NHL to avoid potential inappropriate chronic use and related adverse events.