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Relevant Drug Interactions (relevant + drug_interaction)
Selected AbstractsHigh-throughput screening technologies for drug glucuronidation profilingJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2008Olga Trubetskoy A significant number of endogenous and exogenous compounds, including many therapeutic agents, are metabolized in humans via glucuronidation, catalysed by uridine diphosphoglucurono-syltransferases (UGTs). The study of the UGTs is a growing field of research, with constantly accumulated and updated information regarding UGT structure, purification, substrate specificity and inhibition, including clinically relevant drug interactions. Development of reliable UGT assays for the assessment of individual isoform substrate specificity and for the discovery of novel isoform-specific substrates and inhibitors is crucial for understanding the function and regulation of the UGT enzyme family and its clinical and pharmacological relevance. High-throughput screening (HTS) is a powerful technology used to search for novel substrates and inhibitors for a wide variety of targets. However, application of HTS in the context of UGTs is complicated because of the poor stability, low levels of expression, low affinity and broad substrate specificity of the enzymes, combined with difficulties in obtaining individual UGT isoforms in purified format, and insufficient information regarding isoform-specific substrates and inhibitors. This review examines the current status of HTS assays used in the search for novel UGT substrates and inhibitors, emphasizing advancements and challenges in HTS technologies for drug glucuronidation profiling, and discusses possible avenues for future advancement of the field. [source] Clinically relevant drug interactions of current antifungal agentsMYCOSES, Issue 2 2010Paul O. Gubbins Summary Antifungal agents are often prescribed in critically ill patients who are receiving many other medications. When using systemic antifungals, clinicians may possess susceptibility data and they are typically aware of the potential toxicity of these agents. However, the myriad of potential drugs that antifungal agents can interact with is daunting and can be confusing. This article reviews the pharmacokinetic properties of antifungal agents and their clinically relevant drug interactions. The antifungal agents differ markedly in their pharmacokinetic properties and in how they interact with other medicines. The amphotericin B formulations interact with other medicines primarily by reducing their renal elimination or producing additive toxicities. The azoles interact with other medicines primarily by inhibiting biotransformation or by affecting drug distribution and elimination. The echinocandins have the lowest propensity to interact with other medicines. The clinical relevance of antifungal,drug interactions varies substantially. While certain interactions are benign and result in little or no untoward clinical outcomes, others can produce significant toxicity or compromise efficacy if not properly managed through monitoring and dosage adjustment. However, certain interactions produce significant toxicity or compromise efficacy to such an extent that they cannot be managed and the particular combination of antifungal and interacting medicine should be avoided. [source] Absence of clinically relevant drug interactions following simultaneous administration of didanosine-encapsulated, enteric-coated bead formulation with either itraconazole or fluconazoleBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2002B. Damle Abstract This open-label, two-way crossover study was undertaken to determine whether the enteric formulation of didanosine influences the pharmacokinetics of itraconazole or fluconazole, two agents frequently used to treat fungal infections that occur with HIV infection, and whose bioavailability may be influenced by changes in gastric pH. Healthy subjects were randomized to Treatment A (200-mg itraconazole or 200-mg fluconazole) or Treatment B (same dose of itraconazole or fluconazole with 400 mg of didanosine as an encapsulated, enteric-coated bead formulation). In the itraconazole study, a lack of interaction was concluded if the 90% confidence interval (CI) of the ratio of the geometric means of log-transformed Cmax and AUC0,T values of itraconazole and hydroxyitraconazole, the active metabolite of itraconazole, were contained entirely between 0.75 and 1.33. In the fluconazole study, the equivalence interval for Cmax and AUC0,T was 0.80,1.25. The data showed that for itraconazole the point estimate and 90% CI of the ratios of Cmax and AUC0,T values were 0.98 (0.79, 1.20) and 0.88 (0.71, 1.09), respectively; for hydroxyitraconazole the respective values were 0.91 (0.76, 1.08) and 0.85 (0.68, 1.06). In the fluconazole study, the point estimate and 90% CI of the ratios of Cmax and AUC0,T values were 0.98 (0.93, 1.03) and 1.01 (0.99, 1.03), respectively. The Tmax for itraconazole, hydroxyitraconazole, and fluconazole were similar between treatments. Both studies indicated a lack of clinically significant interactions of the didanosine formulation with itraconazole or fluconazole. These results showed that the encapsulated, enteric-coated bead formulation of didanosine can be concomitantly administered with drugs, such as the azole antifungal agents, whose bioavailability may be influenced by interaction with antacids. Copyright © 2002 John Wiley & Sons, Ltd. [source] Macrolide , induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycinBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2000Jean Frédéric Westphal First page of article [source] | ||||||||||