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Publication : Pharmacokinetics and biodistribution of methotrexate conjugated to mannosyl human serum albumin.

First Author  Sett R Year  1993
Journal  J Antimicrob Chemother Volume  31
Issue  1 Pages  151-9
PubMed ID  8444658 Mgi Jnum  J:12244
Mgi Id  MGI:60494 Doi  10.1093/jac/31.1.151
Citation  Sett R, et al. (1993) Pharmacokinetics and biodistribution of methotrexate conjugated to mannosyl human serum albumin. J Antimicrob Chemother 31(1):151-9
abstractText  The superior efficacy of mannosylated neoglycoprotein-conjugated methotrexate, compared with free drug, in eliminating the parasite burden in both the in-vitro macrophage model and in-vivo mouse model of visceral leishmaniasis has been demonstrated previously. In the present study it was found that: (i) methotrexate conjugated to mannosyl human serum albumin (Man-HSA) was taken up rapidly by the liver and spleen, whereas the free drug was taken up by the kidney; (ii) uptake of the conjugate was ten-fold more efficient in liver macrophages (Kupffer cells) than in hepatocytes; (iii) most of the drug conjugate reached the lysosomes of Kupffer cells; and (iv) the active drug was released in the lysosomes of macrophages to act on Leishmania parasites.
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