Systemic Lupus Erythematosus Activity Affects the Sinusoidal Uptake Transporter OATP1B1 Evaluated by the Pharmacokinetics of Atorvastatin

摘要: The present study assessed the effect of systemic lupus erythematosus (SLE) activity, a chronic and inflammatory autoimmune disease, on sinusoidal uptake transporter OATP1B1 using atorvastatin (ATV) as probe drug. Fifteen healthy subjects, 13 patients with controlled SLE (SLEDAI 0-4), 12 uncontrolled from 6 to 15), all women, were investigated. Apparent total clearance midazolam (MDZ), marker CYP3A4 did not vary among three investigated groups. groups showed higher plasma concentrations MCP-1 TNF-α, while group also IL-10. area under curve (AUC) for ATV (60.47 (43.76-83.56) vs. 30.56 (22.69-41.15) ng⋅hour/mL) its inactive metabolite ATV-lactone (98.74 (74.31-131.20) 49.21 (34.89-69.42) ng⋅hour/mL), lower apparent (330.7 (239.30-457.00) 654.5 (486.00-881.4) L/hour) volume distribution (2,609 (1,607-4,234) 7,159 (4,904-10,450) L), when compared subjects (geometric mean 95% confidence interval). pharmacokinetics metabolites differ between subject group. In conclusion, increased exposure both ATV-lactone, inferring inhibition once in vivo activity by oral MDZ was unaltered. state, disease itself, responsible changes described consequence OATP1B1, because altered SLE.