Drug interactions studies

Reports of Hepatic Metabolism and Drug Interaction Studies... 

Before an antiviral agent becomes a drug, advanced toxicity testing, pharmacological combination, and drug-interaction studies are needed. The use of new cell-based assays that can predict mitochondrial toxicity, lactic acidosis, peripheral neuropathy, anemia, hypersensitivity, lipodystrophy, and other potential side effects can alleviate these issues (Stuyver et al. 2002). 

Human pharmacology (Phase I) Assess tolerance Define/describe pharmacokinetics and pharmacodynamics Explore drug metabolism and drug interactions Estimate activity Dose-tolerance studies Single and multiple dose PK and/or PD studies Drug interaction studies... 

Source Center for Drug Evaluation and Research. Guidance for Industry, Drug Metabolism/Drug Interaction Studies in the Drug Development Process Studies In Vitro, FDA, Rockville, MD, 1997, http //www.fda.gov/cder/guidance/clin3.pdf [accessed September 20,2007]. 

What are the ADME characteristics of the drug For drugs that are metabolised, there are a number of enzyme inhibitors and inducers which may potentially affect the same pathway. Selection of a drug interactions study at the level of hepatic metabolism is becoming much more rational... 

There are several factors to take into account in the design of drug interaction studies. Singledose studies have been criticised but may be useful to exclude major effects. If an interaction is detected with single doses, it maybe necessary to conduct a study at steady state, mimicking the dosage used in clinical practice to determine the true clinical consequences of interaction. 

Explore drug metabohsm and drug interactions Estimate activity Drug interaction studies... 

Huang, S.M., Temple, R., Throckmorton, D.C. and Lesko, L.J. (2007) Drug interaction studies study design, data analysis, and implications for dosing and labeling. Clinical Pharmacology and Therapeutics, 81, 298-304. 

Mahmood I, Green MD. Drug interaction studies of therapeutic proteins or monoclonal antibodies. J Chn Pharmacol 2007 47 1540. 

No drug interaction studies have been conducted in humans. Animal studies indicate no change in the clearance or toxicity of either methotrexate or anakinra when the two agents are administered together. Concomitant administration of a TNF blocker appears to increase the risk of serious infection. The response to vaccines may be diminished in patients taking anakinra. 

No formal drug interaction studies of oseltamivir have been performed. Oseltamivir and its carboxylate metabolite do not interact with the cytochrome P450 system. Although probenecid decreases the elimination of oseltamivir, dosage adjustment is not required during coadministration of these drugs because of oseltamivir s margin of safety. Oseltamivir does not interfere with antibody production in response to the influenza vaccine. 

Drug interactions No formal drug interaction studies of darbepoetin with other medications commonly used in chronic renal failure patients have been performed. 

Drug interactions No drug interaction studies have been conducted with Avonex. Other interferons have been found to reduce cytochrome P-450-mediated drug metabolism. Hepatic microsomes isolated from Avonex-treated rhesus monkeys showed no influence on hepatic P-450 enzyme metabolism activity. 

Drug interactions No clinical drug interaction studies have been conducted. 

Drug interactions No formal drug interaction studies in human subjects have been conducted. Studies in rats did not demonstrate changes in the clearance of methotrexate or anakinra when the two drugs were administered together. 

Drug interactions No formal drug interaction studies have been conducted with Rebif. Monitoring patients for neutropenia and lymphopenia is required if Rebif is given in combination with myelo-suppressive agents. 

Drug interactions The label states that no pharmacokinetic-based drug-drug interaction studies have been conducted with Synarel. However, because nafarelin acetate is a peptide that is primarily degraded by peptidase and not by cytochrome P-450 enzymes, drug interactions would not be expected to occur. 

Drug interactions No formal drug-drug interaction studies have been conducted. The following medications have been administered in clinical trials with Simulect with no incremental increase in adverse reactions azathioprine, corticosteroids, cyclosporine, mycophenolate mofetil, and muromonab-CD3. 

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