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In Vitro and In Silico Identification and Characterization of Thiabendazole as a Mechanism-based Inhibitor of CYP1A2 and Simulation of Possible Pharmacokinetic Drug-drug Interactions Blog Post

Thiabendazole (TBZ) and its major metabolite 5-hydroxythiabendazole (5OH-TBZ) were screened for potential time-dependent inhibition (TDI) against CYP1A2. Screen assays were carried out in the absence and presence of NADPH. TDI was observed…

Towards a Quantitative Framework for the Prediction of DDIs Arising from Cytochrome P450 Induction Blog Post

Although CYP induction is not generally considered to be as clinically relevant as CYP inhibition, there are important examples where induction has caused both therapeutic failure, due to insufficient exposure…

Bioavailability and Tolerability of Intranasal Diazepam in Healthy Adult Volunteers Blog Post

Intranasal therapy has been proposed as an alternative for the management of seizure emergencies. The bioavailability, dose proportionality and tolerability of a supersaturated intranasal formulation of diazepam (DZP) solubilized in…

Enhancement of Oral Bioavailability of Insulin in Humans Blog Post

OBJECTIVE:The purpose of this study is to investigate oral absorption of 1, 2 and 3 U/kg oral insulin five test products with different particle sizes in comparison with 0.1 U/kg…

Quantitative Evaluation of Pharmacokinetic Inhibition of CYP3A Substrates by Ketoconazole: A Simulation Study Blog Post

The US Food and Drug Administration draft drug interaction guidance recommends that 400 mg ketoconazole (KTZ) be administered once daily for several days (QD400) for maximal CYP3A inhibition. Some investigators suggest that a…

Mechanism-based Inhibition of Cytochrome P450 Enzymes: An Evaluation of Early Decision-making In Vitro Approaches and Drug-drug Interaction Prediction Methods Blog Post

The ability to use in vitro human cytochrome P450 (CYP) time-dependent inhibition (TDI) data for in vivo drug-drug interaction (DDI) predictions should be viewed as a prerequisite to generating the data. Important terms in making such predictions are kinact and KI but…

Population Pharmacokinetics of Intravenous Pantoprazole in Pediatric Intensive Care Patients Blog Post

What is already known about this subject The use of intravenous pantoprazole, a proton pump inhibitor, has been increasing in the paediatric intensive care unit. Despite this increased use, data…

Metabolism of Dextrorphan by CYP2D6 in Different Recombinantly Expressed Systems and Its Implications for the In Vitro Assessment of Dextromethorphan Metabolism Blog Post

Cytochrome P450 2D6 (CYP2D6) mediated formation of dextrorphan (DOR) from dextromethorphan (DEX) is widely used as a marker to assess the activity of this enzyme both in vitro and in…

More Than Numbers: The Power of Graphs in Meta-analysis Blog Post

In meta-analysis, the assessment of graphs is widely used in an attempt to identify or rule out heterogeneity and publication bias. A variety of graphs are available for this purpose….

Pharmacokinetic Predictions in Children by Using the Physiologically-based Pharmacokinetic Modeling Blog Post

Nowadays, 50-90% of drugs used in children have never been actually studied in this population. Consequently, either our children are often exposed to the risk of adverse drug events or to lack of efficacy,…

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