Effects of ABCB1, UGT1A1, and UGT1A9 Genetic Polymorphisms on the Pharmacokinetics of Sitafloxacin Granules in Healthy Subjects.

Clinical Pharmacology in Drug Development
Lu-Ning SunYong-Qing Wang

Abstract

Sitafloxacin, a new fluoroquinolone, has strong antibacterial activity. We evaluated the effects of sitafloxacin granules in single-dose and multidose cohorts and the effects of ABCB1, UGT1A1, and UGT1A9 genetic polymorphisms on the pharmacokinetics (PK) of sitafloxacin in healthy subjects. The single-dose study included 3 fasted cohorts receiving 50, 100, and 200 mg of sitafloxacin granules and 1 cohort receiving 50 mg of sitafloxacin granules with a high-fat meal. The multidose study included 1 cohort receiving 100 mg of sitafloxacin granules once daily for 5 days. PK parameters were calculated using noncompartmental parameters based on concentration-time data. The genotypes for ABCB1, UGT1A1, and UGT1A9 single-nucleotide polymorphisms were determined using Sanger sequencing. Subsequently, the association between sitafloxacin PK parameters and target single-nucleotide polymorphisms was analyzed. Sitafloxacin granules were well tolerated up to 200 and 100 mg in the single-dose and multidose studies, respectively. Sitafloxacin AUC and Cmax increased linearly within the detection range, and a steady state was reached within 3 days after the administration of multiple oral doses. Our findings showed that Cmax was lower in the ABC...Continue Reading

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