International Journal of Pharmacology1811-77751812-5700Asian Network for Scientific Information10.3923/ijp.2008.431.442MoazedB. HiebertL. M.6200846The aim of this study was to determine if the stomach
is a site for low molecular heparin (LMWH) absorption. Gastric mucosa
was mounted in a Vertical Diffusion Ussing Chamber and the LMWHs, tinzaparin
or reviparin, were added to the mucosal buffer at pH 7.4 or 4.0. Potential
difference (PD), resistance and short circuit current (Isc) were measured
across the mucosa. Buffers and tissues were analyzed for chemical LMWH
and anti-factor Xa activity. The PD became more negative on LMWH addition
when the mucosal side was compared to the serosal side. The PD returned
to baseline following a lag period, which was greater at pH 4.0 versus
7.4. Changes in resistance were similar to those for PD. Isc increased
with time at pH 7.4 but not pH 4.0, which was most dramatic for reviparin.
LMWHs were recovered from serosal buffer and tissue and had anti-factor
Xa activity at both pH 7.4 and 4.0 although amounts found in serosal buffer
and rate of movement were greater at pH 7.4 versus 4.0. In conclusion,
changes in PD, LMWH recovery and anti-factor Xa activity in serosal buffer
indicate that LMWHs cross rat gastric mucosa. Changes in Isc suggest that
active transport may depend on mucosal pH. Furthermore, LMWHs cross gastric
mucosa under both neutral and acidic conditions, however transport is
faster in a neutral environment suggesting that the stomach, with an acidic
environment, may not be the main site for LMWH absorption in vivo.]]>Andersson, L.O., T.W. Barrowcliffe, E. Holmer, E.A. Johnson and G.E. Sims,19769575583Ayalon, A., M.J. Sanders, L.P. Thomas, D.A. Amirian and A.H. Soll,19827970097013Chao, A.C., J.H. Widdicombe and A.S. Verkman,1990113193202Cooke, H.J. and D.C. Dawson,1978234E257E261Eastman, I.M. and E.G. Miller,1935110255262Faaij, R.A., N. Srivastava, J.M. van-Griensven, R.C. Schoemaker and C. Kluft et al.,199954929935Fareed, J., D. Hoppensteadt, C. Schultz, Q. Ma and M.F. Kujawski et al.,2004Pharmacologic heterogeneity in low molecular weight heparins. Impact on the therapeutic profile.]]>10983999Fareed, J., Q. Ma, M. Florian, J. Maddineni and O. Iqbal et al.,20037357377Fareed, J., W.L. Leong, D. Hoppenstead, W.P. Jeske and J. Walenga et al.,200430703713Hiebert, L.M., S.M. Wice and T. Ping,200458372380Hiebert, L.M., S.M. Wice, L.B. Jaques, K.E. Williams and J.M. Conly,1999133161170Hiebert, L.M., S.M. Wice, T. Ping, D. Herr and V. Laux,200185114118Hiebert, L.M., T. Ping and S.M. Wice,200030196203Hirsh, J., S. Siragusa, B. Cosmi and J. Ginsberg,199574360363Hirsh, J., T.E. Warkentin, R. Raschke, C. Granger and E.M. Ohman et al.,1998114489S510SHurst, R.D., G.H. Ballantyne and I.M. Modlin,199559631635Iqbal, O., S. Aziz, D. Hoppenstead, S. Ahmad and J. Walenga et al.,20016111135Jaques, L.B.,197724203312Jaques, L.B., L.M. Hiebert and S.M. Wice,1991117122130Johnson, E.A., T.B. Kirkwood, Y. Stirling, J.L. Perez-Requejo and G.I. Ingram et al.,197635586591Lasker, S.E.,197552119130Linhardt, R.J. and N.S. Gunay,199925516Lorentsen, K.J., C.W. Hendrix, J.M. Collins, D.M. Kornhauser and B.G. Petty et al.,1989111561566Moazed, B. and L.M. Hiebert,2007in vitro study with an ussing chamber showing that unfractionated heparin crosses rat gastric mucosa.]]>322299305Nickel, J.C., B. Johnston, J. Downey, J. Barkin and P. Pommerville et al.,2000Polysulfate therapy for chronic nonbacterial prostatitis (chronic pelvic pain syndrome category IIIA): A prospective multicenter clinical trial. ]]>56413417Ofosu, F.A.,199824127138Salartash, K., M. Lepore, M.D. Gonze, B.A. Leone and R. Baughman et al.,2000Venous thrombosis.]]>231789794Sue, T.K., L.B. Jaques and E. Yuen,197654613617Vasdev, S., C. Ford, L. Longerich, B. Barrett and S. Parai et al.,199421128Wallon, C., Y. Braaf, M. Wolving, G. Olaison and J.D. Söderholm,200540586595Watanabe, E., M. Takahashi and M. Hayashi,2004in vitro chamber method.]]>58659665Yamashita, S., Y. Tanaka, Y. Endoh, Y. Taki and T. Sakane et al.,1997in vivo drug absorption.]]>14486491Hiebert, L.M., S.M. Wice, T. Ping, R. Hileman and T. Polat et al.,200214C] sucrose octasulfate following oral administration to rats.]]>19838844