Delavirdine mesylate

A potent HIV-1 reverse transcriptase inhibitor with IC50 of 0.26 uM for recombinant HIV-1 RT; exhibits IC50>440 uM for DNA polymerases α and δ; blocks the replication in peripheral blood lymphocytes of 25 primary HIV-1 isolates and has low cellular cytotoxicity; retains significant activity against mutant RTs (K103N, Y181C) .HIV Infection Approved (In Vitro) :Delavirdine has an 50% cytotoxicity at concentrations >100 μM in H9 and PBMC cultures.Delavirdine has low cellular cytotoxicity, causing less than 8% reduction in peripheral blood lymphocyte viability at 100 μM.Delavirdine inhibits HIV-1 reverse transcriptase (RT) wild type with an IC50 value of 0.26 μM, and it inhibits Y181C-substituted RT and K103N-substituted RT with IC50 values of 8.32 uM and 7.7 uM, respectively. (In Vivo) :Delavirdine (U 90152) mesylate (oral gavage; 10 mg/kg, 200 mg/kg, 250 mg/kg; single dose) is absorbed and metabolized rapidly, that it constitutes a minor component in circulation, that its pharmacokinetics are nonlinear, and that its metabolism to desalkyl delavirdine is capacity limited or inhibitable in CD-1 mice (PK study) .