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Pharmacokinetics of eribulin mesylate in cancer patients with normal and impaired renal function.

Tan AR, Sarantopoulos J, Lee L, Reyderman L, He Y, Olivo M, Goel S - Cancer Chemother. Pharmacol. (2015)

Bottom Line: All groups had similar toxicity profiles, with no unexpected adverse events.Renal impairment decreased eribulin clearance and increased exposure.Pharmacokinetic evaluation supports an eribulin dose reduction to 1.1 mg/m(2) in patients with moderate or severe renal impairment.

View Article: PubMed Central - PubMed

Affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.

ABSTRACT

Purpose: To evaluate the effect of renal impairment on eribulin mesylate pharmacokinetics following a single dose in adults with advanced solid tumors.

Methods: Patients were grouped by renal function: moderate impairment (creatinine clearance [CrCl] 30-50 mL/min), severe impairment (CrCl 15-29 mL/min), or normal (CrCl ≥80 mL/min). During each 21-day cycle, eribulin mesylate doses (days 1 and 8) were administered intravenously: moderate, 1.1 mg/m(2) (except cycle 1 day 1, 1.4 mg/m(2)); severe, 0.7 mg/m(2); normal, 1.4 mg/m(2).

Results: Nineteen patients were enrolled (normal, n = 6; moderate, n = 7; severe, n = 6). Renal impairment was associated with an increased mean dose-normalized area under the concentration-time curve (ratios for moderate/normal and severe/normal: 1.49; 90 % confidence interval [CI] 0.9, 2.45). CrCl and renal function correlated positively, with a numerically small slope (0.0184; 90 % CI -0.00254, 0.0394). A simulated dose reduction to eribulin 1.1 mg/m(2) in patients with moderate or severe renal impairment achieved the same exposure as 1.4 mg/m(2) in those with normal renal function. All groups had similar toxicity profiles, with no unexpected adverse events.

Conclusions: Renal impairment decreased eribulin clearance and increased exposure. Pharmacokinetic evaluation supports an eribulin dose reduction to 1.1 mg/m(2) in patients with moderate or severe renal impairment. CLINICALTRIALS.

Gov identifier: NCT01418677.

No MeSH data available.


Related in: MedlinePlus

Individual eribulin plasma clearance (a) and log-transformed dose-normalized Cmax (b), AUC(0–t) (c) and AUC(0–inf) (d) versus creatinine clearance. AUC area under the concentration–time curve, AUC0–t AUC from time 0 to the last measurable concentration, AUC(0–inf) area under the concentration–time curve from time zero extrapolated to infinity, CI confidence interval, CLtot total clearance, Cmax maximum plasma concentration, SE standard error
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Fig2: Individual eribulin plasma clearance (a) and log-transformed dose-normalized Cmax (b), AUC(0–t) (c) and AUC(0–inf) (d) versus creatinine clearance. AUC area under the concentration–time curve, AUC0–t AUC from time 0 to the last measurable concentration, AUC(0–inf) area under the concentration–time curve from time zero extrapolated to infinity, CI confidence interval, CLtot total clearance, Cmax maximum plasma concentration, SE standard error

Mentions: The magnitude of the slope for the linear correlation between eribulin CLtot and renal function (CrCl) was small and the corresponding 90 % CI included zero (0.0184, CI −0.0025, 0.0394) (Fig. 2). The negative slopes for the linear correlations between AUC and Cmax and CrCl were also numerically small and not significant (Fig. 2).Fig. 2


Pharmacokinetics of eribulin mesylate in cancer patients with normal and impaired renal function.

Tan AR, Sarantopoulos J, Lee L, Reyderman L, He Y, Olivo M, Goel S - Cancer Chemother. Pharmacol. (2015)

Individual eribulin plasma clearance (a) and log-transformed dose-normalized Cmax (b), AUC(0–t) (c) and AUC(0–inf) (d) versus creatinine clearance. AUC area under the concentration–time curve, AUC0–t AUC from time 0 to the last measurable concentration, AUC(0–inf) area under the concentration–time curve from time zero extrapolated to infinity, CI confidence interval, CLtot total clearance, Cmax maximum plasma concentration, SE standard error
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612322&req=5

Fig2: Individual eribulin plasma clearance (a) and log-transformed dose-normalized Cmax (b), AUC(0–t) (c) and AUC(0–inf) (d) versus creatinine clearance. AUC area under the concentration–time curve, AUC0–t AUC from time 0 to the last measurable concentration, AUC(0–inf) area under the concentration–time curve from time zero extrapolated to infinity, CI confidence interval, CLtot total clearance, Cmax maximum plasma concentration, SE standard error
Mentions: The magnitude of the slope for the linear correlation between eribulin CLtot and renal function (CrCl) was small and the corresponding 90 % CI included zero (0.0184, CI −0.0025, 0.0394) (Fig. 2). The negative slopes for the linear correlations between AUC and Cmax and CrCl were also numerically small and not significant (Fig. 2).Fig. 2

Bottom Line: All groups had similar toxicity profiles, with no unexpected adverse events.Renal impairment decreased eribulin clearance and increased exposure.Pharmacokinetic evaluation supports an eribulin dose reduction to 1.1 mg/m(2) in patients with moderate or severe renal impairment.

View Article: PubMed Central - PubMed

Affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.

ABSTRACT

Purpose: To evaluate the effect of renal impairment on eribulin mesylate pharmacokinetics following a single dose in adults with advanced solid tumors.

Methods: Patients were grouped by renal function: moderate impairment (creatinine clearance [CrCl] 30-50 mL/min), severe impairment (CrCl 15-29 mL/min), or normal (CrCl ≥80 mL/min). During each 21-day cycle, eribulin mesylate doses (days 1 and 8) were administered intravenously: moderate, 1.1 mg/m(2) (except cycle 1 day 1, 1.4 mg/m(2)); severe, 0.7 mg/m(2); normal, 1.4 mg/m(2).

Results: Nineteen patients were enrolled (normal, n = 6; moderate, n = 7; severe, n = 6). Renal impairment was associated with an increased mean dose-normalized area under the concentration-time curve (ratios for moderate/normal and severe/normal: 1.49; 90 % confidence interval [CI] 0.9, 2.45). CrCl and renal function correlated positively, with a numerically small slope (0.0184; 90 % CI -0.00254, 0.0394). A simulated dose reduction to eribulin 1.1 mg/m(2) in patients with moderate or severe renal impairment achieved the same exposure as 1.4 mg/m(2) in those with normal renal function. All groups had similar toxicity profiles, with no unexpected adverse events.

Conclusions: Renal impairment decreased eribulin clearance and increased exposure. Pharmacokinetic evaluation supports an eribulin dose reduction to 1.1 mg/m(2) in patients with moderate or severe renal impairment. CLINICALTRIALS.

Gov identifier: NCT01418677.

No MeSH data available.


Related in: MedlinePlus