Expert opinion on drug metabolism & toxicology
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Expert Opin Drug Metab Toxicol · Nov 2011
ReviewPharmacokinetic evaluation of pixantrone for the treatment of non-Hodgkin's lymphoma.
Pixantrone is a novel aza-anthracenedione, similar in structure to anthracyclines, including the anthracycline derivative mitoxantrone. There is no standard therapy for relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) in patients who have received two prior lines of therapy. Pixantrone does not bind iron, promotes reactive oxygen species to a lesser degree than other anthracyclines and is therefore believed to be less cardiotoxic without compromising efficacy. ⋯ Pixantrone is an active and safe drug that has been shown to be of benefit when used to treat patients with relapsed aggressive NHL in the context of Phase II and Phase III studies. It was superior to other single-agent therapies in this context and in combination therapy may be the treatment of choice in order to avoid cardiac toxicity. Potentially it is a more effective and less cardiotoxic alternative to doxorubicin in patients with aggressive NHL.
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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.