Gilbertsen R B, Dong M K
Immunopathology, Experimental Therapeutics Dept., Parke-Davis Pharmaceutical Research, Warner-Lambert Co., Ann Arbor, MI 48105, USA.
Adv Exp Med Biol. 1994;370:167-71. doi: 10.1007/978-1-4615-2584-4_37.
Purine nucleosides HxR or GdR (2.5 micrograms/mL blood) were added to EDTA-treated cynomolgus monkey whole blood in vitro, alone or with the PNP inhibitor CI-1000 (1 microgram/mL), mixed, and the concentration of nucleosides remaining in plasma followed as a function of time. The half-lives of GdR and HxR in control blood were 1.2 and < 1 min, respectively, and were extended to 17.8 and 39.8 min, respectively, by coaddition of CI-1000. In contrast, a structural analog of CI-1000, CI-972, when tested in parallel at 1 microgram/mL, had markedly less effect on the breakdown of either nucleoside. The ability of CI-1000 to retard nucleoside breakdown in blood in vitro may be a predictor of in vivo activity, and can be viewed as an early and essential biochemical consequence of PNP inhibition culminating in immunosuppression.
