Article Figures & Data
Figures
- Fig. 1.
DTG metabolism and disposition in hepatocytes. M1, M2, M3, M4, and M5 are the metabolites of DTG. M2 and M3 are formed by UGT1A1 and CYP3A4, respectively. ABCG2 and ABCB1 are the potential transporters mediating the efflux of DTG from hepatocytes to the biliary system. The current work investigated the impact of ABCG2 deficiency on DTG metabolism and pharmacokinetics in mice.
- Fig. 2.
Systemic pharmacokinetics of DTG in WT and Abcg2-null mice. (A and B) Genetic and functional validation of Abcg2-null mice. PPIX was used as a substrate of ABCG2. (C) Serum concentration-time curves of DTG in WT and Abcg2-null mice. The mice were administrated with a single dose of DTG (20 mg/kg, p.o.). (D–G) Comparison of major pharmacokinetic parameters of DTG between WT and Abcg2-null mice. PPIX and DTG were measured by UPLC-QTOFMS. Pharmacokinetic parameters were calculated by noncompartmental model analysis on Phoenix WinNonlin. All data are expressed as means ± S.D. (n = 4). ***P < 0.001 vs. WT. CL, clearance; t1/2, elimination half-life; VZ, volume of distribution.
- Fig. 3.
Tissue-specific pharmacokinetics of DTG in WT and Abcg2-null mice. The mice were administrated with a single dose of DTG (20 mg/kg, p.o.). (A, C, and E) Concentration-time curves of DTG in the liver, kidney, and brain of WT and Abcg2-null mice. (B, D, and F) AUCs of DTG in the liver, kidney, and brain of WT and Abcg2-null mice. AUCs were calculated by Graphpad Prism. All data are expressed as means ± S.D. (n = 4). N.D., not detected.
- Fig. 4.
Excretion of DTG and its metabolites in feces and urine of WT and Abcg2-null mice. Feces and urine were collected overnight from mice treated with a single dose of DTG. (A and B) The abundance of DTG in feces and urine. (C–F) Comparison of DTG and its metabolites in feces and urine. (G and H) Comparison of DTG metabolites between WT and Abcg2-null mice. N.D., not detected. The data (A, B, G, and H) are expressed as means ± S.D. (n = 4).
In this issue
ABCG2 Status and Dose Adjustment of Dolutegravir
