title: ADMET considerations for phosphodiesterase-5 inhibitors.
abstract: BACKGROUND
  ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling is an important aspect of all drug developments. The pharmaceutical industry must always consider ADMET properties in order to optimize drug candidates and to introduce new formulations against existing marketed drugs. Consequently, candidate drug development may be halted early in the discovery phase or during the more costly drug development process because of their poor ADMET properties.
  
  
  METHODS
  The main focus of this article is ADMET profiling, pharmacokinetic (PK) drug interactions, mechanisms and possible adverse drug reactions (ADRs) for approved phosphodiesterase-5 inhibitors (PDE5Is). The authors also look at the efficacy and non-erectogenic benefits of current PDE5Is, which are widely used by patients with erectile dysfunction (ED). The authors also discuss other unapproved PDE5Is such as aildenafil and udenafil, which are currently in use in clinical trials.
  
  
  CONCLUSIONS
  The authors believe that the enhancing effect of PDE5Is on the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway means that PDE5Is could be used to treat various conditions. An important issue in their development is 'cross-talk' between PDE5 and other PDEs and thus their specificity for other PDEs. But while it might be difficult to achieve the ideal ADMET profile, it should not necessarily prevent further development of a lead PDE5I. The risk assessment of PDE5Is, with respect to their ADMET properties, is therefore very important for predicting drug-drug interactions, possible side effects, ADRs and its future clinical applications.
authors: Tehran University of Medical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Department of Toxicology and Pharmacology, Tehran, Iran.
authors: Mohammad Amin
authors: MA
authors: Rezvanfar
authors: Hamid Reza
authors: HR
authors: Rahimi
authors: Mohammad
authors: M
authors: Abdollahi
mesh_terms: D000327:Adsorption; D006152:Cyclic GMP / Q000502:physiology; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D018565:Food-Drug Interactions; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000503:physiopathology; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000503:physiopathology; D006309:Hearing / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006331:Heart Diseases / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics*; D012098:Reproduction / Q000187:drug effects; D014018:Tissue Distribution
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D009569:Nitric Oxide; D006152:Cyclic GMP