Pharmacokinetics and safety of sitafloxacin after single oral doses in healthy volunteers

Wu, Guolan; Wu, Lihua; Hu, Xiurong; Zhou, Haiyan; Liu, Jian; Zhu, Meixiang; Zheng, Yang; Zhai, You; Shentu, Jianzhong

doi:10.5414/cp202147

Cited by 6 publications

(9 citation statements)

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“…The values of PK parameters for single and multiple doses of sitafloxacin were similar. We observed blood concentrations of sitafloxacin with a high DF, and these concentrations rapidly decreased from T max to t. These data were consistent with those of other PK studies of sitafloxacin in Japan and China 6,10,23 …”

Section: Discussionsupporting

confidence: 91%

“…Several studies have previously demonstrated that sitafloxacin is rapidly absorbed after oral administration and has high bioavailability (89%) 7‐9 . The results of a sitafloxacin pharmacokinetic (PK) study in healthy volunteers showed that the cumulative urinary excretion of unchanged sitafloxacin within 48 hours after administration was about 70% 10 . The main metabolite of sitafloxacin is glucuronic acid conjugate, with concentrations of about 30%‐38% in the serum and 5%‐12% in the urine of rats 6,11 .…”

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confidence: 99%

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

Sun

Yang

et al. 2020

Clinical Pharm in Drug Dev

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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 C max 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 C max was lower in the ABCB1 (rs1045642) mutation group, whereas t 1/2 was longer in the UGT1A1 (rs2741049) and UGT1A9 (rs3832043) mutation groups. In conclusion, sitafloxacin granules were safe at single doses and multiple doses up to 200 and 100 mg/day, respectively, with a linear plasma PK profile. However, ABCB1 (rs1045642), UGT1A1 (rs2741049), and UGT1A9 (rs3832043) genetic polymorphisms are likely to influence the C max or t 1/2 and thereby merit further clinical evaluation.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

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

Sun

Yang

et al. 2020

Clinical Pharm in Drug Dev

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“…Accordingly, the C max was 0.72, 1.62 and 2.73 mg/L, respectively, the mean of AUC last was 3.97, 8.71 and 18.03 mg 9h/ L, respectively, and the terminal half-life ranged from 5.19 to 6.28 h (37). Pharmacokinetic studies have also indicated that the C max is rapidly reached after oral administration of 200 mg (0.85-1.3 h) (34,37). Similar values were achieved for epididymal tissue for sitafloxacin 500 mg (36).…”

Section: Discussionmentioning

confidence: 95%

“…Some gastrointestinal adverse effects and a prolongation of the heart‐rate QT‐interval have been described after distribution of 400, 600 or 800 mg daily for 4 days to healthy volunteers . However, the risk of these adverse effects will be very limited when multiple lower doses are administered . Sitafloxacin was rapidly bactericidal and concentration dependent in our time‐kill curves which indicates that high maximum concentration ( C max ) and area under the pharmacokinetic curve (AUC) with a single high dose will be highly efficient .…”

Section: Discussionmentioning

confidence: 96%

“…The C max and AUC have been shown to be proportional to the doses after oral administration of sitafloxacin 50, 100 and 200 mg. Accordingly, the C max was 0.72, 1.62 and 2.73 mg/L, respectively, the mean of AUC last was 3.97, 8.71 and 18.03 mg ×h/L, respectively, and the terminal half‐life ranged from 5.19 to 6.28 h . Pharmacokinetic studies have also indicated that the C max is rapidly reached after oral administration of 200 mg (0.85–1.3 h) .…”

Section: Discussionmentioning

confidence: 99%

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In vitro activity and time‐kill curve analysis of sitafloxacin against a global panel of antimicrobial‐resistant and multidrug‐resistant Neisseria gonorrhoeae isolates

Jönsson

Golparian

Hamasuna

et al. 2017

APMIS

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J€ onsson A, Foerster S, Golparian D, Hamasuna R, Jacobsson S, Lindberg M, Jensen JS, Ohnishi M, Unemo M. In vitro activity and time-kill curve analysis of sitafloxacin against a global panel of antimicrobial-resistant and multidrug-resistant Neisseria gonorrhoeae isolates. APMIS 2018; 126: 29-37 Treatment of gonorrhoea is a challenge worldwide because of emergence of resistance in N. gonorrhoeae to all therapeutic antimicrobials available and novel antimicrobials are imperative. The newer-generation fluoroquinolone sitafloxacin, mostly used for respiratory tract infections in Japan, can have a high in vitro activity against gonococci. However, only a limited number of recent antimicrobial-resistant isolates from Japan have been examined. We investigated the sitafloxacin activity against a global gonococcal panel (250 isolates cultured in 1991-2013), including multidrug-resistant geographically, temporally and genetically diverse isolates, and performed time-kill curve analysis for sitafloxacin. The susceptibility to sitafloxacin (agar dilution) and seven additional therapeutic antimicrobials (Etest) was determined. Sitafloxacin was rapidly bactericidal, and the MIC range, MIC 50 and MIC 90 was ≤0.001-1, 0.125 and 0.25 mg/L, respectively. There was a high correlation between the MICs of sitafloxacin and ciprofloxacin; however, the MIC 50 and MIC 90 of sitafloxacin were 6-fold and >6-fold lower, respectively. Sitafloxacin might be an option for particularly dual antimicrobial therapy of gonorrhoea and for cases with ceftriaxone resistance or allergy. However, further in vitro and particularly in vivo evaluations of potential resistance, pharmacokinetics/pharmacodynamics and ideal dosing for gonorrhoea, as well as performance of randomized controlled clinical, trials are crucial.

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A randomized, controlled, multicenter clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus moxifloxacin in adult patients with community-acquired pneumonia

Zhu

Peng

et al. 2021

Current Medical Research and Opinion

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Objectives: To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP). Patients and methods: This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.cn identifier: CTR20130046). CAP patients received sitafloxacin tablets 100mg once daily (qd) or 100mg twice daily (bid) to compare with moxifloxacin tablets 400mg qd, for 7-10 days. The primary outcome was non-inferiority of sitafloxacin to moxifloxacin in clinical cure rate at test of cure (TOC) visit in per-protocol set (PPS). Results: A total of 343 patients were randomized (sitafloxacin 100mg qd, n=117, sitafloxacin 100mg bid, n=116, moxifloxacin, n=110), 291 patients were included in PPS (sitafloxacin 100mg qd, n=96, sitafloxacin 100mg bid, n=94, moxifloxacin, n=101). The clinical cure rate was 94.8% in sitafloxacin 100mg qd group, 96.8% in sitafloxacin 100mg bid group, and 95.0% in moxifloxacin group. At TOC visit, the microbiological success rate was 97.0% (32/33) in sitafloxacin 100mg qd group, 97.1% (34/35) in sitafloxacin 100mg bid group, and 94.9% (37/39) in moxifloxacin group in microbiological evaluable set (MES). The incidence of study drug-related adverse events (AEs) was 23.3% (27/116) in sitafloxacin 100mg qd group, 29.8% (34/114) in sitafloxacin 100mg bid group, and 28.2% (31/110) in moxifloxacin group (P> 0.05). The common AEs related to study drug were dizziness, nausea, diarrhea, increased A c c e p t e d M a n u s c r i p t platelet count, and ALT elevation. All the AEs resolved completely after discontinuation of study drug. Conclusion: Sitafloxacin 100mg qd or 100mg bid for 7-10 days is not inferior to moxifloxacin 400mg qd for 7-10 days in the clinical efficacy for adult CAP patients. Sitafloxacin provides safety profile comparable to moxifloxacin.

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Pharmacokinetics and safety of sitafloxacin after single oral doses in healthy volunteers

Abstract: In healthy Chinese subjects, single dosing of sitafloxacin resulted in linear plasma pharmacokinetics.

Cited by 6 publications

References 0 publications

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

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

In vitro activity and time‐kill curve analysis of sitafloxacin against a global panel of antimicrobial‐resistant and multidrug‐resistant Neisseria gonorrhoeae isolates

A randomized, controlled, multicenter clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus moxifloxacin in adult patients with community-acquired pneumonia

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