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Does Hepatic Impairment Affect the Exposure of Monoclonal Antibodies?

Qin Sun1, Shirley Seo2, Simbarashe Zvada3

  • 1Division of Infectious Disease Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.

Clinical Pharmacology and Therapeutics
|January 4, 2020
PubMed

Limited information is available regarding the effect of hepatic impairment (HI) on the pharmacokinetics of monoclonal antibodies (mAbs). The results of an earlier report based on therapeutic proteins, including mAbs, approved through the end of 2012 were inconclusive due to limited HI data available at that time. New HI data for mAbs or antibody-drug conjugates (ADCs; with a focus on the mAb component) available between 2013 and 2018 were evaluated. The investigation indicates there is almost no data for severe HI, limited data for moderate HI, and abundant data for mild HI. A significant exposure decrease was found for several mAbs or ADCs and a trend for decreasing area under the concentration-time curve (AUC) was observed for other mAbs. Multiple potential mechanisms may contribute to the exposure decrease. Dose may need to be adjusted for patients with HI, after taking into account the exposure-response relationships for both efficacy and safety.

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