Expert opinion on drug metabolism & toxicology
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Expert Opin Drug Metab Toxicol · Jun 2016
ReviewPharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol.
A variety of medications are used for symptom control in palliative care, such as morphine, midazolam and haloperidol. The pharmacokinetics of these drugs may be altered in these patients as a result of physiological changes that occur at the end stage of life. ⋯ The pharmacokinetics of drugs in terminally ill patients can be complex and limited evidence exists on guided drug use in this population. To improve the quality of life of these patients, more knowledge and more pharmacokinetic/pharmacodynamics studies in terminally ill patients are needed to develop individualised dosing guidelines. Until then knowledge of pharmacokinetics and the physiological changes that occur in the final days of life can provide a base for dosing adjustments that will improve the quality of life of terminally ill patients. As the interaction of drugs with the physiology of dying is complex, pharmacological treatment is probably best assessed in a multi-disciplinary setting and the advice of a pharmacist, or clinical pharmacologist, is highly recommended.
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Expert Opin Drug Metab Toxicol · May 2016
ReviewPharmacodynamics and pharmacokinetics of sodium zirconium cyclosilicate [ZS-9] in the treatment of hyperkalemia.
Hyperkalemia is a common electrolyte disorder that arises from dysfunctional homeostatic mechanisms or as a consequence of decreased renal function. Sodium zirconium cyclosilicate (ZS-9) is a potential new therapy for hyperkalemia in both acute and chronic settings. ⋯ ZS-9 has a unique mechanism of action consisting of thermodynamically favorable sequestration of potassium ions, enabling rapid trapping and removal of excess potassium. The potassium lowering action of ZS-9 is predictable and rapid, leading to significant reduction of serum potassium within 1 hour of administration by irreversibly eliminating excess potassium rather than acting via intracellular translocation. Its safety profile, including gastrointestinal events, has been generally similar to that of placebo, with the exception of infrequent but manageable events of peripheral edema and transient hypokalemia. ZS-9 has demonstrated potential for enabling renin-angiotensin-aldosterone system inhibitors in mid-term studies, with long-term studies ongoing.
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Expert Opin Drug Metab Toxicol · Jan 2016
ReviewPharmacokinetic and pharmacodynamic evaluation of sublingual sufentanil in the treatment of post-operative pain.
Intravenous patient-controlled analgesia using opioids is frequently used to provide perioperative analgesia. However, there are a number of drawbacks for intravenous patient-controlled analgesia. The sufentanil sublingual tablet system is a major evolution in technology and drug development for postoperative pain management. ⋯ The sufentanil sublingual tablet system can decrease intravenous patient-controlled analgesia-related safety issues. Current clinical studies have demonstrated this novel system to be safe and effective in postoperative pain management.
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Expert Opin Drug Metab Toxicol · Jul 2015
ReviewNeonatal medicines research: challenges and opportunities.
The key feature of the newborn is its fast age-dependent maturation, resulting in extensive variability in pharmacokinetics and -dynamics, further aggravated by newly emerging covariates like treatment modalities, environmental issues or pharmacogenetics. This makes clinical research in neonates relevant and needed, but also challenging. ⋯ Challenges relating to neonatal medicine research can largely be overcome. Tailored tools and legal initiatives, combined with clever trial design will result in more robust information on neonatal pharmacotherapy. This necessitates collaborative efforts between clinical researchers, sponsors, regulatory authorities, and last but not least patient representatives and society.
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Expert Opin Drug Metab Toxicol · Jul 2015
ReviewTools for predicting the PK/PD of therapeutic proteins.
Assessments of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics are an integral part in the development of novel therapeutic agents. Compared with traditional small molecule drugs, therapeutic proteins possess many distinct PK/PD features that necessitate the application of modified or separate approaches for assessing their PK/PD relationships. ⋯ A variety of state-of-the-art PK/PD tools is currently being applied and has been adjusted to support the development of proteins as therapeutics, including allometric scaling approaches, target-mediated disposition models, first-in-man dose calculations, physiologically based PK models and empirical and semi-mechanistic PK/PD modeling. With the advent of the next generation of biologics including bioengineered antibody constructs being developed, these tools will need to be further refined and adapted to ensure their applicability and successful facilitation of the drug development process for these novel scaffolds.