title: Pharmacokinetics of cyclodextrins and drugs after oral and parenteral administration of drug/cyclodextrin complexes.
abstract: OBJECTIVE
  The objective of the present study was to shed some light on pharmacokinetics of cyclodextrins (CDs) and drugs after oral and parenteral administration of inclusion complexes.
  
  
  RESULTS
  The complex binding constant in water can predict pharmacokinetics after parenteral administration, but it has to be considered in the context of the physiological environment, where plasma proteins compete with CDs for drug binding. Neither drug/CD nor drug/protein complexes can extravasate, but differently from proteins, CDs are readily cleared through glomerular filtration. In such intricate interrelationships, for complexes with low-to-mid binding constant, binding of drug to plasma proteins will mainly dictate the pharmacokinetics. Oppositely, for drugs showing large CD complex binding constant and low protein binding, significant decrease in distribution volume and enhanced excretion of unmetabolized drug are observed; thus, relevant changes in bioavailability can be predicted. In the case of oral administration, volume for dilution/dissolution of the complexes is relatively low and hence excess CD can hamper drug absorption from the gastrointestinal (GI) tract.
  
  
  CONCLUSIONS
  CDs are well-established multipurpose excipients for overcoming organoleptic and biopharmaceutical deficiencies of a variety of drugs. Balances between free and complexed drug in the GI tract and between drug-CD binding and drug-protein binding in plasma seem to play a relevant role in drug pharmacokinetics.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Thorsteinn
authors.initials: T
authors.lastname: Loftsson
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Moya-Ortega
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez-Lorenzo
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Concheiro
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001667:Binding, Competitive; D003505:Cyclodextrins / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D065569:Gastrointestinal Absorption; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D003505:Cyclodextrins; D005079:Excipients; D004364:Pharmaceutical Preparations; D014867:Water
keywords: bioequivalence; clearance; drug pharmacokinetics; drug-CD complex; oral permeability