International Journal of Pharmacology1811-77751812-5700Asian Network for Scientific Information10.3923/ijp.2015.351.358KimDae-Jun RyuHyun-Mo ParkSang-in ParkSoo-Jin SongChang-Hyun KuSae-Kwang 42015114Ondansetron is used mainly as an antiemetic in emetogenic cancer chemotherapy
and radiotherapy and post-operative nausea and vomiting (NV). However, recent
study recommend reducing ondansetron dose because of possible life-threaten cardiotoxicity
problems. Ijintang-gamibang (IJTGMB) is a polyherb complex, a famous traditional
digestive drug in Korean medicine, which has shown the protective and functional
benefits in gastrointestinal impairments. Therefore, the influences of IJTGMB
on ondansetron pharmacokinetics were examined for the combination therapy. One
batch of rats received single dosing of ondansetron with IJTGMB (combination)
or ondansetron with distilled water (control). The IJTGMB or distilled water was
co-administered orally within 5 min after ondansetron. Another batch of rats received
repeated dosing of the combination for 8 days after pretreatments with IJTGMB
for 6 days or the control for 8 days after pretreatments with distilled water
for 6 days. The plasma samples were analyzed by various pharmacokinetic parameters
including T max, C max, AUC, t 1/2 and MRT
inf. In the single dosing, plasma concentration of ondansetron was not different
between the combination and control and the pharmacokinetic parameters were not
different between the both treatments. In the initial treatment of the repeated
dosing after the pretreatments, the kinetics of ondansetron concentration and
the pharmacokinetic parameters showed no differences between the both treatments.
It suggests little influences of IJTGMB on ondansetron pharmacokinetics in single
dosing with or without pretreatments with IJTGMB. However, after repeated dosing
for 8 days, ondansetron in plasma was detected lower and longer in the combination
than control. In addition, among the parameters assessed here, AUC of ondansetron
was significantly reduced in combination compared to control, meaning reduced
bioavailability of ondansetron by repeated co-administration with IJTGMB for 8
days. These may provide useful information for proper dosing regimen of the novel
combination therapy.]]>Roila, F., A. Del Favero, R.J. Gralla and M. Tonato,19989811819Bailer, A.J.,198816303309Beck, T.M., A.A. Ciociola, S.E. Jones, W.H. Harvey and N.S. Tchekmedyian et al.,1993118407413Bozigian, H.P., J.F. Pritchard, A.E. Gooding and G.E. Pakes,19948310111013Cagnoni, P.J., S. Matthes, T.C. Day, S.I. Bearman, E.J. Shpall and R.B. Jones,19992414Charbit, B., J.C. Alvarez, E. Dasque, E. Abe, J.L. Demolis and C. Funck-Brentano,2008109206212Chiou, W.L.,19786539546Cho, J.Y., J. Park, E.S. Yoo, K. Yoshikawa, K.U. Baik, J. Lee and M.H. Park,1998Coptis japonica var. dissecta on tumor necrosis factor-alpha production in lipopolysaccharide-stimulated raw264.7 cells.]]>211216Choi, H.B.,2010316481De Alwis, D.P., L. Aarons and J.L. Palmer,199846117125Dershwitz, M., P.M. di Biase, C.E. Rosow, R.S. Wilson, P.E. Sanderson and A.F. Joslyn,199277447452Dershwitz, M., C.E. Rosow, P.M. di Biase, A.F. Joslyn and P.E. Sanderson,19925296101DeVane, C.L.,19834201201Doggrell, S.A. and J.C. Hancox,201312421431Donnerer, J.,2003Pages: 233Pages: 233Dursteler, C., A. Mases, V. Fernandez, O. Pol and M.M. Puig,200610629638Figg, W.D., G.E. Dukes, J.F. Pritchard, D.J. Hermann and H.R. Lesesne et al.,199636206215Gilbert, C.J., W.P. Petros, J. Vredenburgh, A. Hussein and M. Ross et al.,199842497503Gralla, R.J., D. Osoba, M.G. Kris, P. Kirkbride and P.J. Hesketh et al.,19991729712994Hafermann, M.J., R. Namdar, G.E. Seibold and R.L. Page,201135358Henriksson, R., H. Lomberg, G. Israelsson, B. Zackrisson and L. Franzen,199231767769Hospira Inc.,20092009Jann, M.W., T.L. ZumBrunnen, S.N. Tenjarla, E.S. Ward Jr. and D.J. Weidler,199818288294Ji, H.F., X.J. Li and H.Y. Zhang,200910194200Jordan, K., R. Gralla, F. Jahn and A. Molassiotis,2014722197202Kanauchi, O., T. Iwanaga, A. Andoh, Y. Araki and T. Nakamura et al.,200116160168Lee, C.J., J.H. Lee, J.H. Seok, G.M. Hur, Y.C. Park, I.C. Seol and Y.H. Kim,200369523526Lewis, D.F.V., Y. Ito, P.J. Eddershaw, M. Dickins and P.S. Goldfarb,201042530Li, C.Q., L.C. He and J.Q. Jin,200721347353Lien, C.A., F. Gadalla, T.T. Kudlak, P.B. Embree, G.J. Sharp and J.J. Savarese,19935399403Markham, A. and E.M. Sorkin,199345931952Martin, C., V. Roman, D. Agay and M. Fatome,1998149631636McKechnie, K. and A. Froese,201057453457Milne, R.J. and R.C. Heel,199141574595Mondick, J.T., B.M. Johnson, L.J. Haberer, M.E. Sale and P.C. Adamson et al.,2010667786Murren, J.R., S.A. DiStasio, A. Lorico, A. McKeon and E.G. Zuhowski et al.,20006256265Oh, J.H., B.S. Kim, H.Y. Lim, D.W. Lim and B.H. Choi et al.,2005Ljintang-gamibang).]]>26641654Ok, M.J., S.D. Park and H.I. Lee,2002231125Preston, G.C., O.N. Keene and J.L. Palmer,199651827830Resch, M., A. Steigel, Z.L. Chen and R. Bauer,199861347350Roila, F. and A. del Favero,19952995109Satoh, K., F. Nagai and I. Kano,2000+, K+-ATPase by hinesol, a major component of So-jutsu, by interaction with enzyme in the E1 state.]]>59881886Scheid, V.,20092nd Edn.,Scuderi, P., B. Wetchler, Y.F. Sung, M. Mingus and S. DuPen et al.,1993781520Simpson, K.H. and F.M. Hicks,199648774781Tamaro, G., G.M. Danek, M.A. Mangiarotti, P. Tamaro and G.A. Zanazzo,1995255555Yang, S.H. and M.G. Lee,200829414426Ye, J.H., R. Ponnudurai and R. Schaefer,20013 receptor antagonist and its applications in CNS-related disorders.]]>7199213Yoshizawa, M., K. Yokoyama, Y. Nakano and H. Nakamura,2004124571575Zhou, S., Y. Gao, W. Jiang, M. Huang, A. Xu and J.W. Paxton,2003353598