title: Anthranoid laxatives influence the absorption of poorly permeable drugs in human intestinal cell culture model (Caco-2).
abstract: Interactions between widely used anthranoid laxatives and other simultaneously administered drugs are not known. In this paper, the influence of rhein, danthron, sennidins A/B, sennosides A/B, and senna leaf infusion was investigated on the permeability of furosemide, ketoprofen, paracetamol, propranolol, verapamil, digoxin, and Rhodamine 123 across Caco-2 monolayers. The effects on monolayer integrity ([(14)C]mannitol permeability, TEER) were also determined. The in vitro absorption of highly permeable drugs was not strongly affected during co-administration of the laxatives. Furosemide permeability was enhanced by rhein and danthron (3.6 and 3.0-fold), which may partly be due to opening of the paracellular spaces and/or effects on active efflux. However, the secretory permeability of digoxin and Rho 123 was not strongly affected by rhein and danthron, suggesting that inhibition of MDR1 was not responsible for the increased permeation of furosemide. The absorptive permeability of digoxin was decreased by rhein and danthron, offering evidence for effects on apical membranes. The effects on monolayer integrity were detectable, but reversible. According to presented experiments, daily use of laxatives with well-absorbing drugs would seem unlikely to affect drug permeability, but the effects on the absorption of poorly permeable drugs cannot be excluded.
authors.affiliation: Drug Discovery and Development Technology Center (DDTC), Faculty of Pharmacy, University of Helsinki, Finland. leena-laitinen@msn.com
authors.forename: Leena
authors.initials: L
authors.lastname: Laitinen
authors.forename: Elina
authors.initials: E
authors.lastname: Takala
authors.forename: Heikki
authors.initials: H
authors.lastname: Vuorela
authors.forename: Pia
authors.initials: P
authors.lastname: Vuorela
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Kaukonen
authors.forename: Martti
authors.initials: M
authors.lastname: Marvola
mesh_terms: D000042:Absorption / Q000187:drug effects; D000082:Acetaminophen / Q000493:pharmacokinetics; D000880:Anthraquinones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001628:Beverages / Q000032:analysis; D018938:Caco-2 Cells; D002250:Carbon Radioisotopes; D002400:Cathartics / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004077:Digoxin / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D007660:Ketoprofen / Q000493:pharmacokinetics; D008353:Mannitol / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D011433:Propranolol / Q000493:pharmacokinetics; D012676:Senna Extract / Q000737:chemistry; D000081226:Sennosides; D014700:Verapamil / Q000493:pharmacokinetics
chemical_list: D000880:Anthraquinones; D002250:Carbon Radioisotopes; D002400:Cathartics; D000081226:Sennosides; D000082:Acetaminophen; D008353:Mannitol; D004077:Digoxin; D005665:Furosemide; D012676:Senna Extract; D007660:Ketoprofen; D011433:Propranolol; D014700:Verapamil; C020491:rhein; C004315:danthron