Eribulin mesylate exhibits 49–65% protein binding at concentrations of 100–1000 ng/mL. After the administration of eribulin mesylate 0.25–4 mg/m2, the mean volume of distribution is 43–114 L/m2. Eribulin exhibits linear pharmacokinetics, with a rapid distribution phase followed by a slow elimination phase. The mean terminal half-life is 40 hours. Eribulin is primarily metabolized by cytochrome P-450 (CYP) isoenzyme 3A4 to at least four inactive metabolites. Approximately 5–7% of the eribulin dose is excreted unchanged in the urine, with an estimated 82% excreted fecally as unchanged drug. In patients with hepatic impairment, clearance is reduced and the elimination half-life prolonged compared with patients with normal hepatic function. Eribulin does not appear to affect the metabolism of other therapeutic agents by CYP3A4, and current data suggest that eribulin does not inhibit the metabolism of concurrently administered drugs that are metabolized by CYP3A4, suggesting a minimal risk of drug–drug interactions in the clinical setting.
In a pharmacokinetic study, the eribulin area under the concentration– time curve (AUC) was increased 1.8- and 2.5-fold in patients with mild (Child-Pugh class A, n = 7) and moderate (Child-Pugh class B, n = 5) hepatic impairment, respectively, compared with patients with normal hepatic function. In addition, eribulin mesylate doses of 1.1 and 0.7 mg/m2 administered to patients with mild and moderate hepatic impairment, respectively, resulted in eribulin exposure similar to that seen in patients with normal hepatic function who received a eribulin mesylate dose of 1.4 mg/m2. This suggests that empirical dose reductions are necessary in this population (Table 1).[21,23]
In patients with moderate renal impairment (CLcr, 30–50 mL/min), the AUC of eribulin was increased 2-fold compared with patients with normal renal function. With the increase in AUC, the suggested empirical starting dose for patients with moderate renal impairment is 1.1 mg/m2. The use of eribulin in patients with severe renal impairment (CLcr, <30 mL/min) has not been studied; however, further dose reductions are likely necessary in this population (Table 1).
Am J Health Syst Pharm. 2012;69(9):745-755. © 2012 American Society of Health-System Pharmacists
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