title: Recent Pharmacokinetic Studies in Combination Therapies for Diabetes and Related Vascular Complications.
abstract: BACKGROUND
  Combination treatment has been a popular therapeutic strategy in diabetes and related vascular complications. However, the reasonable dosing regimen in combination treatment remains unknown. Nowadays, pharmacokinetics (PK) is becoming a useful approach to reveal the mechanisms of drug-drug interactions (DDIs) and reasonable drug compatibility in combination treatment.
  
  
  METHODS
  This article reviews the pharmacokinetics studies on combination therapies for diabetes and its vascular complications to reveal the mechanisms of reasonable drug compatibility for optimizing drug combination treatment.
  
  
  METHODS
  Relevant articles were identified through the PubMed search (from January 2006 to December 2012) in English and the CNKI and Wan Wei websites in Chinese (from January 2000 to December 2012).
  
  
  RESULTS
  Thirty-six articles were identified, including 15 on DDIs, 8 on pharmacological mechanism or metabolic pathways, and 6 on non-drug factors. DDIs studies showed the changes of drug-effect in combination treatment, which could guide physicians to administer anti-hyperglycemic agent in best time and in optimal order. PK studies based on pharmacological mechanism or metabolic pathways revealed reasonable compatibility of fixed-dose combination (FDC). A combination of pharmacokinetics/pharmacodynamics (PK/PD) and population pharmacokinetics (PopPK) and the development of PK/PD models in PK studies were good ways to determine the rational use and treatment effects in combined therapies. There were other 7 PK studies on the compatibility of preparations in Chinese medicine, which also outlined the features of DDIs in herbal drugs.
  
  
  CONCLUSIONS
  PK studies may be useful to resolve the growing and complex issue of drug combinations to devise reasonable treatment regimens and to make physicians recognize the mechanisms of combined therapies. However, more longterm, comprehensive PK studies on combination therapy should be conducted in future.
authors.forename: He-Qi
authors.initials: HQ
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, 38 Xueyuan Rd, HaiDian District, Beijing, 100191, China. luwei_pk@bjmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Kun-Jie
authors.initials: KJ
authors.lastname: Yang
authors.forename: Zhi-Geng
authors.initials: ZG
authors.lastname: Li
mesh_terms: D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008954:Models, Biological
chemical_list: D002317:Cardiovascular Agents; D007004:Hypoglycemic Agents