Expert opinion on drug metabolism & toxicology
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Expert Opin Drug Metab Toxicol · May 2021
ReviewThe impact of continuous renal replacement therapy on antibiotic pharmacokinetics in critically ill patients.
Introduction: Mortality due to severe infections in critically ill patients undergoing continuous renal replacement therapy (CRRT) remains high. Nevertheless, rapid administration of adequate antibiotic therapy can improve survival. Delivering optimized antibiotic therapy can be a challenge, as standard drug regimens often result in insufficient or excessive serum concentrations due to significant changes in the volume of distribution and/or drug clearance in these patients. ⋯ We have provided explanations for the changes in the PKs of antibiotics observed and suggestions to optimize dosage regimens in these patients. Expert opinion: Despite considerable efforts to identify optimal antibiotic dosage regimens for critically ill patients receiving CRRT, adequate target achievement remains too low for hydrophilic antibiotics in many patients. Whenever possible, individualized therapy based on results from therapeutic drug monitoring must be given to avoid undertreatment or toxicity.
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Expert Opin Drug Metab Toxicol · Dec 2019
ReviewPharmacokinetic and pharmacodynamic considerations for NMDA-receptor antagonist ketamine in the treatment of chronic neuropathic pain: an update of the most recent literature.
Introduction: Chronic neuropathic pain (NP) is an incapacitating illness caused by a lesion of the somatosensory nervous system and is associated with several diseases or syndromes. Since current treatment options lack adequate efficacy in the majority of patients, ketamine is often administered to treat refractory NP. Areas covered: This review gives an overview of new ketamine pharmacokinetic data including data on intranasal and inhaled ketamine. ⋯ Expert opinion: Proof of sustained, large effects of ketamine in the treatment of NP from randomized controlled clinical trials is lacking, although we cannot exclude selective ketamine efficacy in patients with central sensitization, opioid-induced hyperalgesia or opioid tolerance. Interestingly, data from observational trials and case series do suggest the efficacy of ketamine in producing effective pain relief in NP with positive patient-related outcome measures. Additional randomized trials in often ill-defined groups of chronic pain patients are not useful and we suggest to conduct future studies in NP patients with central sensitization and/or with opioid refractory severe NP.
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Expert Opin Drug Metab Toxicol · Jun 2019
Meta Analysis Comparative StudyMonoclonal antibodies in severe asthma: is it worth it?
Background: To date, there is the strong need to compare the efficacy across the monoclonal antibodies (mAbs) approved to treat severe asthma. Research design and method: A quantitative synthesis has been performed to compare the impact of omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and placebo on the risk of exacerbation and change in forced expiratory flow in 1 s (FEV1) in severe asthmatic patients. Results: All the investigated mAbs were more effective than placebo in reducing the risk of exacerbation and improving lung function. ⋯ The overall-marked placebo effect indicates that a better adherence to drug regimens in the context of RCTs may lead to noteworthy improvement in the clinical condition of severe asthmatic patients. Conclusions: Further extensive meta-analyses are needed to identify the factors influencing the efficacy profile of mAbs in severe asthma. This may also permit to identify the profile of patients that are specifically responsive to either anti-IgE, anti-IL-4Rα, anti-IL-5, or anti-IL-5Rα mAbs.
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Expert Opin Drug Metab Toxicol · May 2019
ReviewVenetoclax in the treatment of chronic lymphocytic leukemia.
Venetoclax, an antagonist of BCL-2 protein plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL). It has been approved by the FDA for the treatment of relapsed/refractory CLL with del17p, and by the EMA for patients with del17p/TP53 mutation who have failed a BCR inhibitor, or in patients without those aberrations who have failed previous therapy, regardless of their genetic/molecular profile. Venetoclax in combination with rituximab has been also approved for the treatment of CLL after at least 1 prior therapy, regardless of del17p. ⋯ The proceedings of the American Society of Hematology held during the last five years were also included. Expert opinion: Venetoclax shows high efficacy, a favorable toxicity profile, and a high rate of minimal residual disease negativity, which is thought to have an impact on overall survival. It is efficient in patients with del17p/TP53 mutations, the incidence of which increases during clonal CLL evolution, and after the failure of BCR pathway inhibitors.