title: Sotalol permeability in cultured-cell, rat intestine, and PAMPA system.
abstract: OBJECTIVE
  To clarify sotalol's classification in the BCS versus BDDCS systems through cellular, rat everted sac and PAMPA permeability studies.
  
  
  METHODS
  Studies were carried out in Madin Darby canine kidney (MDCK) and MDR1-transfected MDCK (MDCK-MDR1) cell lines, rat everted gut sacs and the Parallel Artificial Membrane Permeability Assay (PAMPA) system. Three-hour transport studies were conducted in MDCK cell lines (with apical pH changes) and MDCK-MDR1 cells (with and without the P-glycoprotein inhibitor GG918); male Sprague-Dawley rats (300~350 g) were used to prepare everted sacs. In the PAMPA studies, drug solutions at different pH's were dosed in each well and incubated for 5 h. Samples were measured by LC-MS/MS, or liquid scintillation counting and apparent permeability (P(app)) was calculated.
  
  
  RESULTS
  Sotalol showed low permeability in all of the cultured-cell lines, everted sacs and PAMPA systems. It might be a border line P-glycoprotein substrate. The PAMPA study showed that sotalol's permeability increased with a higher apical pH, while much less change was found in MDCK cells.
  
  
  CONCLUSIONS
  The low permeability rate for sotalol correlates with its Class 3 BDDCS assignment and lack of in vivo metabolism.
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Hideaki
authors.initials: H
authors.lastname: Okochi
authors.forename: Leslie Z
authors.initials: LZ
authors.lastname: Benet
authors.forename: Suo-Di
authors.initials: SD
authors.lastname: Zhai
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors; D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D002460:Cell Line; D002463:Cell Membrane Permeability; D004285:Dogs; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D008297:Male; D008567:Membranes, Artificial; D051381:Rats; D017207:Rats, Sprague-Dawley; D013015:Sotalol / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D008567:Membranes, Artificial; D013015:Sotalol