Expert opinion on drug metabolism & toxicology
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Expert Opin Drug Metab Toxicol · May 2013
Contribution of oxycodone and its metabolites to the overall analgesic effect after oxycodone administration.
Oxycodone (OC) is an opioid which exerts its analgesic effect through µ-receptors in the brain. It is metabolized through CYP450 enzymes and some of the metabolites show pharmacological activity. The aim of this investigation is to research the contribution of the metabolites of OC to its overall analgesic effect. A further aim was to elucidate the role of drug-drug interactions and CYP2D6 polymorphism. ⋯ This article's calculations demonstrate that OC itself is responsible for the analgesic effect. Although OM and noroxymorphone have much higher µ-receptor affinity than the parent drug, the metabolite concentrations at the site of action are very low. This suggests that there is a minimal analgesic effect from these metabolites.
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Expert Opin Drug Metab Toxicol · Apr 2013
ReviewPharmacokinetic and pharmacodynamic considerations for the current chronic constipation treatments.
Chronic constipation is a frequent condition often treated pharmacologically. The laxatives available belong to very different pharmacologic groups. ⋯ The most relevant laxative groups are the older representatives osmotic salts, sugars and sugar alcohols, macrogol, anthraquinones, diphenolic laxatives or diphenyl methanes (bisacodyl and sodium picosulfate) and the newer compounds prucalopride, lubiprostone and linaclotide. For all of these laxatives efficacy has been shown in controlled trials. Electrolyte losses do not occur when laxatives are given in therapeutic doses (rare exceptions with phosphate salts and salinic laxatives). The older laxatives are also safe regarding teratogenicity, abortion and lactation. For the newer compounds no respective data are available as yet. It is questionable whether the newer compounds offer advantages over the older ones. Unfortunately, comparative trials are lacking.
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Expert Opin Drug Metab Toxicol · Apr 2013
ReviewUnderstanding the pharmacokinetics of anxiolytic drugs.
Anxiety disorders are considered the most common mental disorders and they can increase the risk for comorbid mood and substance use disorders, significantly contributing to the global burden of disease. For this reason, anxiolytics are the most prescribed psychoactive drugs, particularly in the Western world. ⋯ There is a need for a more balanced assessment of the benefits and risks associated with benzodiazepine use, particularly considering pharmacokinetic profile of the drugs to ensure that patients, who would truly benefit from these agents, are not denied appropriate treatment. An optimal pharmacological approach involving an integrative pharmacokinetic and pharmacodynamic optimization strategy would ensure better treatment and personalization of anxiety disorders. So it would be desirable for the development of new anxiolytic drug(s) that are more selective, fast acting and free from the unwanted effects associated with the traditional benzodiazepines as tolerance or dependence.
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Expert Opin Drug Metab Toxicol · Dec 2012
ReviewEtoricoxib and the treatment of ankylosing spondylitis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line therapies in the management of patients with ankylosing spondylitis. This chronic inflammatory skeletal disorder, a subtype of spondyloarthritis, is characterized by inflammatory back pain and affects young adults causing important suffering and disability. Long-term use of conventional NSAIDs is associated with a risk of gastrointestinal complications. Etoricoxib is a specific cyclooxygenase 2 inhibitor with strong anti-inflammatory effects and a favorable pharmacokinetic profile for the management of inflammatory disorders. The drug has been associated with reduced severe gastrointestinal adverse events. However, the cardiovascular safety of cyclooxygenase 2 inhibitors has been debated. ⋯ Etoricoxib is useful in the first-line management of ankylosing spondylitis patients. Its anti-inflammatory effects and relative protection against severe gastrointestinal side effects should be balanced with negative effects on the cardiovascular system and an overall subjective tolerance not better than that of conventional NSAIDs. Whether etoricoxib will also become a mainstay in the prevention of structural damage in ankylosing spondylitis is not yet clear.
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Expert Opin Drug Metab Toxicol · Nov 2012
ReviewPharmacokinetic and pharmacodynamic considerations for NMDA receptor antagonists in the treatment of chronic neuropathic pain.
Chronic neuropathic pain is a debilitating disease caused by a lesion of the somatosensory nervous system. The N-methyl-D-aspartate receptor (NMDAR) plays an important role in the development of this pain state. Proof of efficacy of NMDAR inhibitors in treating neuropathic pain is limited, with the non-selective NMDAR antagonist ketamine being most effective. ⋯ More proof from good-quality randomized clinical trials on the efficacy of NMDAR inhibitors is required. A major advantage of ketamine therapy is the ability of the molecule to induce rapid and potent antidepressant effects. This is relevant taken the fact that chronic pain and depression are closely linked and are often present in the same patient.