title: Intestinal permeability of forskolin by in situ single pass perfusion in rats.
abstract: The intestinal permeability of forskolin was investigated using a single pass intestinal perfusion (SPIP) technique in rats. SPIP was performed in different intestinal segments (duodenum, jejunum, ileum, and colon) with three concentrations of forskolin (11.90, 29.75, and 59.90 µg/mL). The investigations of adsorption and stability were performed to ensure that the disappearance of forskolin from the perfusate was due to intestinal absorption. The results of the SPIP study indicated that forskolin could be absorbed in all segments of the intestine. The effective permeability (P (eff)) of forskolin was in the range of drugs with high intestinal permeability. The P (eff) was highest in the duodenum as compared to other intestinal segments. The decreases of P (eff) in the duodenum and ileum at the highest forskolin concentration suggested a saturable transport process. The addition of verapamil, a P-glycoprotein inhibitor, significantly enhanced the permeability of forskolin across the rat jejunum. The absorbed fraction of dissolved forskolin after oral administration in humans was estimated to be 100 % calculated from rat P (eff). In conclusion, dissolved forskolin can be absorbed readily in the intestine. The low aqueous solubility of forskolin might be a crucial factor for its poor oral bioavailability.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, China.
authors.forename: Zhen-Jun
authors.initials: ZJ
authors.lastname: Liu
authors.forename: Dong-bo
authors.initials: DB
authors.lastname: Jiang
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Tian
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Yin
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Huang
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Weng
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D031330:Coleus / Q000737:chemistry*; D005576:Colforsin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003106:Colon / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D008297:Male; D010477:Perfusion / Q000379:methods; D010539:Permeability; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics; D031346:Plectranthus / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology
chemical_list: D010936:Plant Extracts; D005576:Colforsin; D014700:Verapamil