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PIII-3Dose-escalating study to investigate safety, tolerability, and pharmacokinetics of lonicera japonica extract in healthy volunteers by J KIM; K LIM; J KIM; B KIM; J JEON; O CHUNG; Y TAE; J CHO; K YU; S SHIN is a Medicine article available to read on EtoBox.
What is PIII-3Dose-escalating study to investigate safety, tolerability, and pharmacokinetics of lonicera japonica extract in healthy volunteers about?
AIM: We studied the involvement of P-glycoprotein (P-gP) in the transepithelial transport of the two enantiomers of tramadol (TMD) and that of its active metabolite O-desmethyl-tramadol (M1). METHODS: We used the human intestinal Caco-2 cell monolayer model. Transmission electron microscopy (TEM), transepithelial electrical resistance (TEER), [ 3 H]-mannitol permeability, Western blot analysis and bidirectional transport of rhodamine 123 were performed to assess the integrity of the model. Bidirectional transport of 1, 10, 50 and 100M of racemic TMD and M1 across the Caco-2 monolayers was investigated in the presence and absence of the P-gP inhibitor cyclosporine (10M). TMD and M1 quantitation was performed using respectively a chiral and non-chiral HPLC method. RESULTS: We found that: i) (ϩ)-TMD, (Ϫ)-TMD and M1 showed a statistically significant differential transport between the basolateral-to-apical (B-A) and apical-to-basolateral (A-B) direction (apparent permeability coefficient Papp(B-A)/(A-B): 2-2.5); ii) A-B transport was not affected by cyclosporine but B-A transport was slightly increased in the presence of the inhibitor by 6 to 18% for TMD (ϩ) and (Ϫ) and 14 to 26% for M
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- Author
- J KIM; K LIM; J KIM; B KIM; J JEON; O CHUNG; Y TAE; J CHO; K YU; S SHIN
- Publisher
- Nature Publishing Group; Wiley (Blackwell Publishing); Wiley-Blackwell; Wiley; Springer Science and Business Media LLC; Research Square (ISSN 0009-9236)
- Published
- 2006
- Language
- EN
- Field
- Medicine (Health Sciences)
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