Expert opinion on drug metabolism & toxicology
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Migraine is the most common painful neurological disorder, affecting 13% of the general population. Triptans represent a powerful pharmacological tool in acute migraine treatment, however, a significant portion of treated patients cannot have access to this class due to possible adverse affects. Today, a total of seven triptan molecules are available, representing a commonly prescribed migraine treatment. Although there is a need of extensive use of triptans, only 25% of migraine patients are using triptans. ⋯ Frovatriptan has been developed in order to improve safety and efficacy of triptans. It shows a favorable tolerability and efficacy profile, limited to 24/48-h headache recurrence, when compared with other triptans. Preclinical data suggest that the pharmacokinetic profile of frovatriptan may differ from other available triptans. In fact, among triptans, frovatriptan showed the highest potency at the 5-HT1B receptor (8.2) and the longer half-life (26 h). These parameters determine the clinical properties of frovatriptan; in particular the lowest rate of headache recurrence in comparison with other triptans.
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Expert Opin Drug Metab Toxicol · Nov 2011
ReviewTriazole antifungal agents drug-drug interactions involving hepatic cytochrome P450.
Triazole antifungal agents are often prescribed as first-line therapy for candidemia, in non-neutropenic hosts and invasive pulmonary aspergillosis, and in critically ill patients who receive many concomitant medications. As substrates and inhibitors of cytochrome P450 (CYP), the triazoles can interact with many drugs, which may lead to enhanced toxicity of the concomitant medication(s) or ineffective antifungal treatment. Therefore, clinicians must understand the drug interaction profile of this class. ⋯ Triazoles interact with many drugs and the primary mechanism for these interactions is hepatic CYP. Many studies published in the past 2 decades characterize these interactions using the state-of-the-art methods of the time. However, advances in genotyping, improved analytical technology and bioanalytical methods, which enable accurate molecular identification and stereochemical analysis, have substantially added to the understanding of the role hepatic CYP plays in triazole-drug interactions in humans.
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Expert Opin Drug Metab Toxicol · Nov 2011
ReviewPharmacokinetic and pharmacodynamic evaluation of tigecycline.
As the spread of multidrug-resistant (MDR) and extensive drug-resistant (XDR) organisms constitutes a real threat for patients, new antimicrobials are needed. Tigecycline, the first-in-class glycylcycline, possesses an extended spectrum of antimicrobial activity including MDR and XDR organisms, which holds promise as a treatment option beyond currently approved indications and deserves expanded evaluation of its pharmacokinetics/pharmacodynamics (PK/PD). ⋯ Tigecycline remains one of our last resorts against MDR pathogens; its clear role has to be re-defined through intense PK/PD applications; dose escalation and exploration of combinations with other antibiotics seem to be the first step towards an expansion of its currently approved indications. The lung remains the most controversial and challenging site regarding the PK/PD standpoint due to the predominance of Acinetobacter baumannii and carbapenemase-producing Klebsiella pneumoniae among ventilator-associated pneumonia infections, for which tigecycline is mostly used off-label.
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Expert Opin Drug Metab Toxicol · Sep 2011
ReviewMetabolic and toxicological considerations for diuretic therapy in patients with acute heart failure.
Diuretics are widely recommended in patients with acute heart failure (AHF). However, loop diuretics predispose patients to electrolyte imbalance and hypovolemia, which in turn leads to neurohormonal activation and worsening renal function (WRF). Unfortunately, despite their widespread use, limited data from randomized clinical trials are available to guide clinicians with the appropriate management of this diuretic therapy. ⋯ Data from several large registries that evaluated diuretic therapy in hospitalized patients with AHF suggest that its efficacy is far from being universal. Further studies are warranted to determine whether high-dose diuretics are responsible for WRF and a higher rate of coexisting renal disease are instead markers of more severe heart failure. The authors believe that monitoring congestion during diuretic therapy in AHF would refine the current approach to AHF treatment. This would allow clinicians to identify high-risk patients and possibly reduce the incidence of complications secondary to fluid management strategies.
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Expert Opin Drug Metab Toxicol · Jun 2011
ReviewPain management in the 21st century: utilization of pharmacogenomics and therapeutic drug monitoring.
Anesthesiologists and pain management physicians recognize that the key to clinical success is the ability to effectively control pain and related symptoms in patients without causing excess side effects from prescribed medications. The use of opioids for pain management is broadly accepted by regulatory bodies, professional organizations (i.e., the WHO) and physicians, as is the wide range of patient responses to these medications. Pharmacogenomics and therapeutic drug monitoring are two underutilized tools which can be implemented to best predict and monitor which opioid and dose may be the most appropriate for an individual patient. ⋯ In the end, the authors strongly believe that objective tools such as pharmacogenomics and therapeutic drug monitoring provide added benefit (minimizing adverse effects, while maximizing efficacy) and will ultimately advance the practice of pain management by incorporating these tools into the standard of care.