Fig. 5: Pharmacokinetics.

SD rats were administered a single IM dose of NM1TFV (green), NM2TFV (orange), or NTAF (blue) (75 mg/kg TFV-eq.) to determine pharmacokinetic (PK) profiles. a Prodrug (left) and TFV (right) concentrations in blood were determined at days 1 and 14 then every two weeks for 8 weeks (***P = 0.0001, *P = 0.0177 NM1TFV vs. NM2TFV prodrug). Tissue biodistribution of M1TFV, M2TFV, and TFV was assessed at 28 and 56 days after injection in the b liver (*P = 0.0107, **P = 0.002 NM1TFV vs. NM2TFV prodrug; ****P < 0.0001, ***P = 0.0007 NM1TFV vs. NM2TFV TFV), c spleen (**P = 0.0034, ****P < 0.0001 NM1TFV vs. NM2TFV prodrug; **P = 0.004, **P = 0.0055, NM1TFV vs. NM2TFV TFV), d lymph node (***P = 0.0009 NM1TFV vs. NM2TFV prodrug; ***P = 0.0001, ****P < 0.0001 NM1TFV vs. NM2TFV TFV), e gut (***P = 0.0006, ***P = 0.0007 NM1TFV vs. NM2TFV prodrug; ****P < 0.0001 NM1TFV vs. NM2TFV TFV), and f site of injection (**P = 0.0043 NM1TFV vs. NM2TFV prodrug; **P = 0.0084, **P = 0.0085 NM1TFV vs. NM2TFV TFV). Data are expressed as mean ± SEM where N = 4 biological replicates. Prodrug concentrations were compared using two-tailed unpaired t-test (****P < .0001, ***P < .001, **P < .01, *P < .05 NM1TFV compared with NM2TFV). To compare TFV levels between three or more groups, ordinary one-way ANOVA followed by Tukey’s post hoc test with a single pooled variance was used (****P < .0001, ***P < .001, **P < .01, *P < .05 NM1TFV compared with NM2TFV).