Document Detail

Formulation approaches in mitigating toxicity of orally administrated drugs.
MedLine Citation:
PMID:  23317423     Owner:  NLM     Status:  In-Data-Review    
This paper provides an overview of current formulation approaches to mitigate toxicity of orally administrated drugs. The formulation approaches are characterized by their intended impact on a drug's pharmacokinetic parameters, pharmacological properties or metabolic pathways. Regulatory opportunities and constraints with focus on U.S. regulations in optimizing a drug's safety or efficacy profile are reviewed. The following formulation approaches are described: (i) pharmacokinetic-modulating and (ii) pharmacodynamic-modulating. In the pharmacokinetic-modulating approach, the pharmacokinetic profile of drug release is modified by, for example, a reduction in peak drug plasma concentration while preserving or improving AUC, thereby potentially reducing toxic effects that may be related to C(max). In the pharmacodynamic-modulating approach, the drug is co-dosed with pharmacologically active or nonpharmacologically active agent or agents intended for mitigation of the drug's toxicity. The pharmacodynamic-modulating approach requires information on the specificity of drug interactions with other compounds and also on metabolic pathways. Examples demonstrating successful formulation work in reducing drug toxicity are provided. The in-depth knowledge of the drug's PK and PD properties combined with a greater understanding of the biology of diseases are necessary for successful drug product formulation leading to optimized in vivo exposure and minimized toxicity.
Irina Kadiyala; Elijah Tan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pharmaceutical development and technology     Volume:  18     ISSN:  1097-9867     ISO Abbreviation:  Pharm Dev Technol     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9610932     Medline TA:  Pharm Dev Technol     Country:  England    
Other Details:
Languages:  eng     Pagination:  305-12     Citation Subset:  IM    
Formulation Department, Vertex Pharmaceuticals , Cambridge, MA , USA.
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