[Absorption of papaverine, laudanosine and cepharanthine across human intestine by using human Caco-2 cells monolayers model].
Absorption of papaverine (PAP), laudanosine (LAU) and cepharanthine (CEP) as some chemical constituents of traditional Chinese medicines in human intestine were studied. By using Caco-2 (the human colonic adenocarcinoma cell lines) cell monolayers as an intestinal epithelial cell model, the permeability of PAP, LAU and CEP were studied from apical side (AP side) to basolateral side (BL side) or from BL side to AP side. The three alkaloids were measured by reversed-phase high-performance liquid chromatography coupled with UV detector. Transport parameters and apparent permeability coefficients (Papp) were then calculated and compared with those of propranolol as a control substance of high permeability and atenolol as a control substance of poor permeability. The Papp values of PAP, LAU and CEP were (3.524+/-0.223) x 10(-5), (2.821+/-0.050) x 10(-5) and (6.524+/-0.052) x 10(-5) cm s(-1) from AP side to BL side, and (5.095+/-0.508) x 10(-5), (2.646+/-0.146) x 10(-5) and (5.495+/-0.036) x 10(-5) cm s(-1) from BL side to AP side, respectively. Their Papp values were identical with those of propranolol, which is a transcellular transport marker. On the other hand, the efflux transport of PAP was 1.45 times higher than its influx transport with 0.69 rate of P(app A-->B)/P(app B-->A). But P(app A-->B)/P(app B-->A) values of LAU and CEP were 1.07 and 1.19, respectively, which suggested that the efflux transport have not been involved in their absorbed mechanism in Caco-2 cells monolayers. There is a good correlation between the Papp value and apparent distribution coefficient (Log D) at pH 7.35 for the three alkaloids. PAP, LAU and CEP can be absorbed across intestinal epithelial cells, and they are completely absorbed compounds. PAP may have been involved in efflux mechanism in Caco-2 cells monolayers model from the basolateral-to-apical direction. The O/W (oil/water) partition coefficient plays key role in their transmembrane permeation.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Lian
L
Ma
Xiu-Wei
XW
Yang
D044182:Benzylisoquinolines / Q000032:analysis / Q000302:isolation & purification / Q000493:pharmacokinetics*; D001692:Biological Transport; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D007546:Isoquinolines / Q000032:analysis / Q000302:isolation & purification / Q000493:pharmacokinetics*; D010208:Papaverine / Q000032:analysis / Q000302:isolation & purification / Q000493:pharmacokinetics*; D010946:Plants, Medicinal / Q000737:chemistry; D052117:Benzodioxoles
D044182:Benzylisoquinolines; D007546:Isoquinolines; D010208:Papaverine; C006947:cepharanthine; D052117:Benzodioxoles; C001522:laudanosine