AI Article Synopsis
- The study aimed to analyze the pharmacokinetics of sepantronium (YM155) in Japanese patients with advanced solid tumors and how renal impairment affects its PK profile.
- Thirty-three patients received continuous intravenous infusion of sepantronium, and the analysis categorized renal function based on eGFR values, finding that PK was dose proportional.
- Moderate renal impairment led to increased exposure to sepantronium without affecting the PK parameters in mild renal impairment; no dosage adjustment is needed for mild cases.
Article Abstract
Purpose: The purpose of this analysis was to investigate the pharmacokinetics (PK) of sepantronium (YM155), a small-molecule suppressor of the expression of the antiapoptosis protein survivin, in Japanese patients with advanced solid tumors and to evaluate the effect of renal impairment on the PK profile of sepantronium.
Methods: Sepantronium was administered as a continuous intravenous infusion of 1.8-10.6 mg/m(2)/day for 168 h (7 days) to 33 patients. PK parameters were estimated via non-compartmental method. Renal function was categorized for the analysis based on the chronic kidney disease guidance using eGFR values at pre-dose.
Results: The PK of sepantronium was dose proportional in the dose range of 1.8-10.6 mg/m(2)/day. Age and sex did not significantly affect the PK of sepantronium. Results suggested that total clearance and renal clearance in patients with moderate renal impairment were 0.7-fold lower than those in patients with normal renal function, resulting in 1.3-fold higher steady-state concentration and area under the curve values. The PK parameters of sepantronium in patients with mild renal impairment were comparable to those in the patients with normal renal function.
Conclusions: While age and sex did not significantly affect the PK of sepantronium, moderate renal impairment increased exposure of sepantronium by about 30 %. The results suggest that no dose adjustment is required for patients with mild renal impairment.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428524 | PMC |
| http://dx.doi.org/10.1007/s00280-012-1913-z | DOI Listing |
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