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DRUG-DRUG INTERACTIONS FOR UDP-GLUCURONOSYLTRANSFERASE SUBSTRATES: A PHARMACOKINETIC EXPLANATION FOR TYPICALLY OBSERVED LOW EXPOSURE (AUCI/AUC) RATIOS
Glucuronidation is a listed clearance mechanism for 1 in 10 of the top 200 prescribed drugs. The objective of this article is to encourage those studying ligand interactions withExpand
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Comparison of Different Algorithms for Predicting Clinical Drug-Drug Interactions, Based on the Use of CYP3A4 in Vitro Data: Predictions of Compounds as Precipitants of Interaction
Cytochrome P450 3A4 (CYP3A4) is the most important enzyme in drug metabolism and because it is the most frequent target for pharmacokinetic drug-drug interactions (DDIs) it is highly desirable to beExpand
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Assessment of three human in vitro systems in the generation of major human excretory and circulating metabolites.
An early understanding of key metabolites of drugs is crucial in drug discovery and development. As a result, several in vitro models typically derived from liver are frequently used to study drugExpand
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Atorvastatin Glucuronidation Is Minimally and Nonselectively Inhibited by the Fibrates Gemfibrozil, Fenofibrate, and Fenofibric Acid
Gemfibrozil coadministration generally results in plasma statin area under the curve (AUC) increases, ranging from moderate (2- to 3-fold) with simvastatin, lovastatin, and pravastatin to mostExpand
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Application of CYP3A4 in vitro data to predict clinical drug-drug interactions; predictions of compounds as objects of interaction.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Numerous retrospective analyses have shown the utility of in vitro systems for predicting potential drug-drug interactions (DDIs). Prediction of DDIs from inExpand
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Key considerations in the preclinical development of biosimilars.
Biosimilar development requires several steps: selection of an appropriate reference biologic, understanding the key molecular attributes of that reference biologic and development of a manufacturingExpand
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Reaction phenotyping in drug discovery: moving forward with confidence?
For the pharmaceutical industry, one of the challenges in evaluating the risk of future compound attrition at the discovery stage is the successful prediction of the major routes of clearance inExpand
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Comparative Nonclinical Assessments of the Proposed Biosimilar PF-05280586 and Rituximab (MabThera®)
Comparative nonclinical studies were conducted with the proposed biosimilar PF-05280586 and rituximab-EU (MabThera®). In side-by-side analyses, peptide maps and complement-dependent cytotoxicityExpand
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Comparative Nonclinical Assessments of the Proposed Biosimilar PF-05280014 and Trastuzumab (Herceptin®)
Background and ObjectivesTrastuzumab (Herceptin®) is a humanized monoclonal antibody (mAb) that binds to the HER2 protein. PF-05280014 is being developed as a potential biosimilar to trastuzumabExpand
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Quantitative prediction of renal transporter-mediated clinical drug-drug interactions.
Kidney plays a critical role in the elimination of xenobiotics. Drug-drug interactions (DDIs) via inhibition of renal organic anion (OAT) and organic cation (OCT) transporters have been observed inExpand
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