Assessment of urinary pharmacokinetics and pharmacodynamics of orbifloxacin in healthy dogs with ex vivo modelling

Shimizu, Takefumi; Harada, Kazuki; Manabe, Saki; Tsukamoto, Taku; Ito, Norihiko; Hikasa, Yoshiaki

doi:10.1099/jmm.0.000476

Cited by 6 publications

(13 citation statements)

References 19 publications

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“…T 1/2 in urine was calculated by linear regression of the semi-logarithmic plot of urinary concentration versus the midpoint of the urine collection time [24]. The area under the UBT-versus-time curve within 12 h after administration (AUBT 0-12 ) was calculated as the sum of the products of the reciprocal UBT values and the respective time intervals (h) for each test organism, to easily compare UBT data among the tested strains [22,24,25]. The urinary AUC 0-12 was calculated with the trapezoidal rule by assuming that a drug concentration remains constant in the urinary bladder during each time interval [24].…”

Section: Discussionmentioning

confidence: 99%

“…The area under the UBT-versus-time curve within 12 h after administration (AUBT 0-12 ) was calculated as the sum of the products of the reciprocal UBT values and the respective time intervals (h) for each test organism, to easily compare UBT data among the tested strains [22,24,25]. The urinary AUC 0-12 was calculated with the trapezoidal rule by assuming that a drug concentration remains constant in the urinary bladder during each time interval [24]. The urinary AUC/MIC 0-12 was calculated by dividing the urinary AUC 0-12 by the MIC of the organism.…”

Section: Discussionmentioning

confidence: 99%

“…The UBTs correspond to the maximal dilution titer of urine allowing bactericidal activity for each examined strain and were determined using each dog's urine as previously described [22,24,25]. Each well of the microplates contained 100 µL of the logarithmic serial twofold dilution, ranging from 1:2 to 1:1024, acquired by mixing an equal volume of the urine sample obtained every 4 h after drug administration with the respective individual dog's antimicrobial-free urine obtained prior to drug administration.…”

Section: Determination Of Urinary Bactericidal Titermentioning

confidence: 99%

“…A UBT of 0 was defined as no bactericidal activity, and a UBT of 1 was assigned when only undiluted urine displayed bactericidal activity. UBTs were transformed into ordinal data and described with reciprocal numbers [22,24,25]. Simultaneously with the UBT determination, the absence of growth of the tested organisms was confirmed in all urine samples which had not been inoculated.…”

Section: Determination Of Urinary Bactericidal Titermentioning

confidence: 99%

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Urinary Pharmacokinetic and Pharmacodynamic Profiles of Fosfomycin against Extended-Spectrum β-Lactamase-Producing Escherichia coli with Canine Ex Vivo Modeling: A Pilot Study

et al. 2020

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Fosfomycin is a candidate drug for extended-spectrum β-lactamase (ESBL)-producing bacteria, but its efficacy is yet to be investigated in dogs. This study investigated the urinary pharmacokinetic/pharmacodynamic (PK/PD) profile of fosfomycin orally administered at 80 mg/kg to six healthy dogs to assess its efficacy for canine urinary tract infections (UTIs) caused by ESBL-producing bacteria. Four strains of ESBL-producing Escherichia coli (ESBL-EC) characterized by fosfomycin minimum inhibitory concentrations (MICs) of 0.5, 1, 2, and 32 µg/mL were used. Urine samples for the measurement of urinary drug concentrations and urinary bactericidal titers (UBTs) were obtained after drug administration. The urinary concentrations (µg/mL, mean ± SE) were 1348.2 ± 163.5, 1191.6 ± 260.2, and 661.1 ± 190.4 at 0–4, 4–8, and 8–12 h, respectively, after drug administration. The mean urinary area under the curve during the test period (AUC0–12) of fosfomycin was estimated to be 12,803.8 µg·h/mL. The UBTs for all tested strains fluctuated closely with urine concentration during the test period (r = 0.944–1.000), and the area under the UBT-versus-time curve correlated with the urinary AUC/MIC of each strain (r = 0.991). According to the optimal urinary PK/PD target value, fosfomycin at 80 mg/kg twice daily may be suitable for the treatment of canine UTIs caused by ESBL-EC presenting MIC ≤ 128 µg/mL.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Determination Of Urinary Bactericidal Titermentioning

confidence: 99%

Section: Determination Of Urinary Bactericidal Titermentioning

confidence: 99%

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Urinary Pharmacokinetic and Pharmacodynamic Profiles of Fosfomycin against Extended-Spectrum β-Lactamase-Producing Escherichia coli with Canine Ex Vivo Modeling: A Pilot Study

et al. 2020

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“…These findings indicate that faropenem may be a promising candidate antimicrobial for canine UTIs with ESBL-producing bacteria. However, the urinary pharmacokinetic/pharmacodynamic profile, which is essential for assessment of the treatment efficacy of antimicrobials for UTIs [13][14][15], remains to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Assessment of urinary pharmacokinetic and pharmacodynamic profiles of faropenem against extended-spectrum β-lactamase-producing Escherichia coli with canine ex vivo modelling: a pilot study

Harada

Shimizu

Miyashita

et al. 2019

Access Microbiology

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This study was carried out to investigate the urinary pharmacokinetics and pharmacodynamics of faropenem administered orally at 5 mg kg−1 in six healthy dogs to assess the efficacy of the drug for canine urinary tract infections (UTIs) with extended-spectrum β-lactamase (ESBL)-producing bacteria. Six strains of ESBL-producing Escherichia coli (ESBL-EC) with the following faropenem minimum inhibitory concentrations (MICs) were used: 1 µg ml−1 (n=2), 2 µg ml−1 (n=2), 4 µg ml−1 (n=1) and 16 µg ml−1 (n=1). Urine samples were obtained every 4 h for the first 12 h after administration to measure urinary drug concentration and urinary bactericidal titres (UBTs). Both the urine concentration of faropenem and the UBTs for all tested strains peaked at 0–4 h after administration, and decreased markedly at 8–12 h. The mean urinary concentration of faropenem at 8–12 h (23±5.2 µg ml−1) exceeded the MIC of 1 µg ml−1 by fourfold, which is required to inhibit the growth of 90 % of ESBL-EC. These findings indicate that faropenem administered twice daily at a dose of 5 mg kg−1 is acceptable for the treatment of most dogs with ESBL-EC-related UTIs.

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Assessment of urinary pharmacodynamic profiles of faropenem against extended-spectrum β-lactamase-producing Escherichia coli with canine ex vivo modeling

Harada

Shimizu

Miyashita

et al. 2018

Preprint

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20Extended-spectrum β-lactamase (ESBL)-producing bacteria are of great concern in companion 21 animals with urinary tract infections (UTIs). Because of its high safety and stability in the 22 presence of ESBLs, faropenem is assumed to be a candidate antimicrobial agent for canine UTIs 23 with ESBL-producing bacteria. This study was performed to investigate the urinary 24 pharmacokinetics and pharmacodynamics of faropenem administered at 5 mg/kg body weight in 25 six healthy dogs using an ex vivo model. Six UTI pathogenic strains of ESBL-producing 26 Escherichia coli (ESBL-EC) with the following faropenem minimum inhibitory concentrations 27 (MICs) were used: 1 µg/mL (n = 2), 2 µg/mL (n = 2), 4 µg/mL (n = 1), and 16 µg/mL (n = 1). 28Urine samples were obtained every 4 h for the first 12 h after faropenem administration for 29 measurement of the urine drug concentration and urinary bactericidal titers (UBTs). The urine 30 concentration of faropenem peaked at 0 to 4 h after administration, with a mean maximum 31 concentration of 584 μg/mL, and markedly decreased at 8 to 12 h (23 μg/mL). The median 32 UBTs for all tested ESBL-EC strains were highest at 0 to 4 h and then significantly decreased at 33 8 to 12 h. These findings indicate that administration of faropenem more than once daily is 34 recommended for the treatment of ESBL-EC-related UTIs in dogs. In addition, the median areas 35 under the UBT-time curves (AUBTs) were significantly inversely correlated with the 36 corresponding MICs for faropenem in the tested strains (P < 0.05). Notably, the median AUBTs 37 were significantly higher in ESBL-EC strains with an MIC of 1 µg/mL than in those with an 38 MIC of ≥4 µg/mL (P < 0.05). The present study serves as the basis of clinical application of 39 faropenem for ESBL-producing bacteria-related UTIs in dogs.3 41

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Assessment of urinary pharmacokinetics and pharmacodynamics of orbifloxacin in healthy dogs with ex vivo modelling

Cited by 6 publications

References 19 publications

Urinary Pharmacokinetic and Pharmacodynamic Profiles of Fosfomycin against Extended-Spectrum β-Lactamase-Producing Escherichia coli with Canine Ex Vivo Modeling: A Pilot Study

Urinary Pharmacokinetic and Pharmacodynamic Profiles of Fosfomycin against Extended-Spectrum β-Lactamase-Producing Escherichia coli with Canine Ex Vivo Modeling: A Pilot Study

Assessment of urinary pharmacokinetic and pharmacodynamic profiles of faropenem against extended-spectrum β-lactamase-producing Escherichia coli with canine ex vivo modelling: a pilot study

Assessment of urinary pharmacodynamic profiles of faropenem against extended-spectrum β-lactamase-producing Escherichia coli with canine ex vivo modeling

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