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腎機能低下被験者におけるトピロキソスタット経口投与時の薬物動態および薬力学の検討
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JPY
Abstract
Objectives This study evaluated the pharmacokinetics and pharmacodynamics of topiroxostat in subjects with moderate renal impairment. Methods Topiroxostat was orally administered at a dose of 80 mg to fasting male subjects that were classified as ones with normal renal function(inulin clearance(Cin)≧90 mL/ min/1.73 m2), mild renal impairment group(60≦Cin<90 mL/min/1.73 m2), and moderate renal impairment groups(30≦Cin<60 mL/min/1.73 m2). Thereafter, plasma and urinary concentrations of topiroxostat, its metabolites, and uric acid were determined. Results After topiroxostat administration, the plasma concentrations of unchanged drug exhibited a similar course in each group and reached Tmax at 0.67-1 h, and decreased with T1/2 of 6.7-8.4 hours. As for the pharmacokinetic parameters, there were no significant differences between the mild and moderate renal impairment groups and the normal group. Urinary excretion rate of topiroxostat was<0.1% of the dose in each group within 24 h post dosing. As for plasma concentrations and urinary excretion of metabolites(N-oxide form, N1-glucuronide conjugate, and N2-glucuronide conjugate)after dosing, no remarkable variations were observed in each group. The level of plasma uric acid decreased approximately 1 mg/dL at 24 h after dosing. In addition, the profile of plasma uric acid reduction was similar in each group. Twenty-four hour urinary excretion amounts(Ae0-24)of uric acid decreased from pre-dose values(Ae-24-0)in subjects without renal function. Conclusion Mild and moderate renal impairment affected neither pharmacokinetics nor pharmacodynamics of topiroxostat.
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