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Drug Design, Development and Therapy Volume 10, 2016 - Issue
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Original Research

Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers

Yi-fan Zhang1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
,
Xiao-jian Dai1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
,
Yong Yang1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
,
Xiao-yan Chen1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
,
Ting Wang2 Department of Pharmacy, The First Hospital Affiliated to Lanzhou University, Lanzhou, People’s Republic of China
,
Yun-biao Tang3 Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, People’s Republic of China
,
Cheng-yuan Tsai4 TaiGen Biotechnology Co., Ltd., Taipei, Taiwan
,
Li-wen Chang4 TaiGen Biotechnology Co., Ltd., Taipei, Taiwan
,
Yu-ting Chang4 TaiGen Biotechnology Co., Ltd., Taipei, Taiwan
&
Da-fang Zhong1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of ChinaCorrespondence[email protected]
 show all
Pages 357-370 | Published online: 20 Jan 2016

Figures & data

Table 1 Pharmacokinetic characteristics of nemonoxacin in 12 healthy Chinese volunteers after a single oral dose of 500 mg of nemonoxacin alone or with probenecid

Figure 1 Plasma concentration–time curves for nemonoxacin after a single oral dose of 500 mg of nemonoxacin alone or with probenecid in 12 healthy Chinese volunteers.

Notes: Treatment A, nemonoxacin alone; Treatment B, nemonoxacin with probenecid; data are mean ± standard deviation.
Figure 1 Plasma concentration–time curves for nemonoxacin after a single oral dose of 500 mg of nemonoxacin alone or with probenecid in 12 healthy Chinese volunteers.

Figure 2 Urinary recovery–time curves for nemonoxacin after a single oral dose of 500 mg of nemonoxacin alone or with probenecid in 12 healthy Chinese volunteers.

Notes: Treatment A, nemonoxacin alone; Treatment B, nemonoxacin with probenecid; data are mean ± standard deviation.
Abbreviation: Fe, percentage of the administered dose recovered in the urine.
Figure 2 Urinary recovery–time curves for nemonoxacin after a single oral dose of 500 mg of nemonoxacin alone or with probenecid in 12 healthy Chinese volunteers.

Table 2 Pharmacokinetic properties of nemonoxacin in 12 healthy Chinese volunteers after a single oral dose of 500 mg of nemonoxacin alone or with cimetidine

Figure 3 Plasma concentration–time curves for nemonoxacin after a single oral dose of 500 mg of nemonoxacin alone or with cimetidine in 12 healthy Chinese volunteers.

Notes: Treatment C, nemonoxacin alone; Treatment D, nemonoxacin with cimetidine; data are mean ± standard deviation.
Figure 3 Plasma concentration–time curves for nemonoxacin after a single oral dose of 500 mg of nemonoxacin alone or with cimetidine in 12 healthy Chinese volunteers.

Figure 4 Urinary recovery–time curves for nemonoxacin after a single oral dose of 500 mg of nemonoxacin alone or with cimetidine in 12 healthy Chinese volunteers.

Notes: Treatment C, nemonoxacin alone; Treatment D, nemonoxacin with cimetidine; data are mean ± standard deviation.
Abbreviation: Fe, percentage of the administered dose recovered in the urine.
Figure 4 Urinary recovery–time curves for nemonoxacin after a single oral dose of 500 mg of nemonoxacin alone or with cimetidine in 12 healthy Chinese volunteers.

Figure S1 Product ion spectra of [M + H]+ of nemonoxacin (A) and moxifloxacin (B).

Note: ✧ indicates product ion selected.
Abbreviation: Rel int, relative intensity.
Figure S1 Product ion spectra of [M + H]+ of nemonoxacin (A) and moxifloxacin (B).

Figure S2 Typical chromatograms of nemonoxacin and moxifloxacin (IS) in plasma.

Notes: (A) Blank plasma sample; (B) plasma spiked with 0.005 μg/mL nemonoxacin and 0.4 μg/mL IS; (C) plasma spiked with 0.5 μg/mL nemonoxacin and 0.4 μg/mL IS; and (D) plasma sample 24 hours after oral administration of 500 mg nemonoxacin to a volunteer. Peaks I and II refer to nemonoxacin and IS, respectively.
Abbreviations: IS, internal standard; Rel int, relative intensity.
Figure S2 Typical chromatograms of nemonoxacin and moxifloxacin (IS) in plasma.
Figure S2 Typical chromatograms of nemonoxacin and moxifloxacin (IS) in plasma.

Figure S3 Typical chromatograms of nemonoxacin and moxifloxacin (IS) in urine.

Notes: (A) Blank urine sample; (B) urine spiked with 0.2 μg/mL nemonoxacin and 20.0 μg/mL IS; (C) urine spiked with 8.0 μg/mL nemonoxacin and 20.0 μg/mL IS; and (D) urine sample 24–48 hours after oral administration of 500 mg to a volunteer. Peaks I and II refer to nemonoxacin and IS, respectively.
Abbreviations: IS, internal standard; Rel int, Relative intensity.
Figure S3 Typical chromatograms of nemonoxacin and moxifloxacin (IS) in urine.
Figure S3 Typical chromatograms of nemonoxacin and moxifloxacin (IS) in urine.

Table S1 Precision and accuracy of the LC–MS/MS method to determine nemonoxacin in human plasma or urine (in pre-study validation, n=3 days, six replicates per day)

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