The effect of hepatic insufficiency on the safety and pharmacokinetics of paricalcitol (Zemplar)

Abstract

Background/aims: Paricalcitol is highly protein bound, extensively metabolized and eliminated primarily by hepatobiliary excretion. This study was designed to determine if hepatic disease alters the pharmacokinetics or affects the safety of paricalcitol.

Methods: Subjects with mild (n = 5) or moderate (n = 5) hepatic impairment, and subjects with normal hepatic function (n = 10) enrolled in and completed the study. Each subject was administered a single 0.24 microg/kg intravenous dose of paricalcitol, injected within 1 min.

Results: For both total and unbound paricalcitol, there were no statistically significant differences in the pairwise comparisons between hepatic function groups in paricalcitol concentration at 5 min postdose (C5) or area under the plasma concentration-time curve from time zero to infinity (AUC(0-infinity), except C5 of total paricalcitol between mild and moderate impairment groups (p = 0.02). Paricalcitol binding to plasma proteins was extensive in all hepatic function groups (mean values >99.7%); unbound fraction was greater in subjects with moderate impairment than either healthy subjects or subjects with mild impairment (p < 0.01). Paricalcitol appeared to be well tolerated both by healthy subjects and subjects with mild to moderate hepatic insufficiency.

Conclusion: No adjustment of paricalcitol dose is required for subjects with mild to moderate hepatic impairment. However, caution should be exercised in extrapolating the results from this study to subjects with severe hepatic impairment.