title: Development of an in vitro cell culture model to study milk to plasma ratios of therapeutic drugs.
abstract: OBJECTIVE
  To create an in vitro cell culture model to predict the M/P (concentration of drug in milk/concentration in maternal plasma) ratios of therapeutic drugs viz. rifampicin, theophylline, paracetamol, and aspirin.
  
  
  METHODS
  An in vitro cell culture model using CIT3 cells (mouse mammary epithelial cells) was created by culturing the cells on transwells. The cells formed an integral monolayer, allowing only transcellular transport as it happens in vivo. Functionality of the cells was confirmed through scanning electron microscopy. Time wise transfer of the study drugs from plasma to milk was studied and compared with actual (in vivo) M/P ratios obtained at reported tmax for the respective drugs.
  
  
  RESULTS
  The developed model mimicked two important intrinsic factors of mammary epithelial cells viz. secretory and tight-junction properties and also the passive route of drug transport. The in vitro M/P ratios at reported tmax were 0.23, 0.61, 0.87, and 0.03 respectively, for rifampicin, theophylline, paracetamol, and salicylic acid as compared to 0.29, 0.65, 0.65, and 0.22, respectively, in vitro.
  
  
  CONCLUSIONS
  Our preliminary effort to develop an in vitro physiological model showed promising results. Transfer rate of the drugs using the developed model compared well with the transfer potential seen in vivo except for salicylic acid, which was transferred in far lower concentration in vitro. The model has a potential to be developed as a non-invasive alternative to the in vitro technique for determining the transfer of therapeutic drugs into breast milk.
authors.affiliation: National Institute for Research in Reproductive Health (ICMR), Mumbai, India.
authors.forename: Maithili A
authors.initials: MA
authors.lastname: Athavale
authors.forename: Anurupa
authors.initials: A
authors.lastname: Maitra
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Patel
authors.forename: Vijay R
authors.initials: VR
authors.lastname: Bhate
authors.forename: Villi S
authors.initials: VS
authors.lastname: Toddywalla
mesh_terms: D000082:Acetaminophen / Q000097:blood* / Q000493:pharmacokinetics; D000328:Adult; D000818:Animals; D001241:Aspirin / Q000097:blood* / Q000493:pharmacokinetics; D002460:Cell Line; D005260:Female; D006801:Humans; D051379:Mice; D008895:Milk, Human / Q000378:metabolism*; D008954:Models, Biological; D012293:Rifampin / Q000097:blood* / Q000493:pharmacokinetics; D013806:Theophylline / Q000097:blood* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000082:Acetaminophen; D013806:Theophylline; D001241:Aspirin; D012293:Rifampin
keywords: CIT3 cells; Cell culture; M/P ratios; in vitro; milk-plasma ratio; reversed phase-High performance liquid chromatography