Species-related stereoselective disposition of ofloxacin in the rat, dog and monkey

Okazaki, Osamu; Kurata, Tadashi; Hakusui, Hideo; Tachizawa, Haruo

doi:10.3109/00498259209046656

Cited by 21 publications

(4 citation statements)

References 22 publications

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“…In this context there have been reports of pharmacodynamic differences between R-OFL and S-OFL [31]. For this reason the pharmacokinetics of the enantiomers of OFL might be different.…”

Section: Resultsmentioning

confidence: 99%

HPLC separation and quantification of ofloxacin enantiomers in rabbit plasma. Application to pharmacokinetic studies

et al. 2002

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SummaryA sensitive HPLC method with marbofloxacin (/VlAR) as internal standard and fluorescence detection is described for the analysis of ofloxacin (OFL) enantiomers in plasma samples. Plasma samples were prepared by adding phosphate buffer (pH 7.4, 0.1 M), then extracted with trichloromethane. S-OFL, R-OFL, and the internal standard were separated on a reversed-phase column with water-methanol, 85.5:14.5, as mobile phase. The concentrations of S-OFL and R-OFL eluting from the column (retention times 7.5 and 8.7 min, respectively) were monitored by fluorescence detection with .rex = 331 and -tern = 488 rim. The detection and quantitation limits were 10 and 20 ng mL 1, respectively, for 5-OFL and 11 and 21 ng mL 1 for R-OFL. Response was linearly related to concentration in the range 10 to 2500 ng mL 1. Recovery was close to 93% for both compounds. The method was applied to determination of the enantiomers of OFL in plasma samples collected during pharmacokinetic studies.

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“…In this context there have been reports of pharmacodynamic differences between R-OFL and S-OFL [31]. For this reason the pharmacokinetics of the enantiomers of OFL might be different.…”

Section: Resultsmentioning

confidence: 99%

HPLC separation and quantification of ofloxacin enantiomers in rabbit plasma. Application to pharmacokinetic studies

et al. 2002

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“…Considering that LFX represents the 50% of any dose of ofloxacin and the lack of enantioselectivity in all pharmacokinetic processes (Okazaki, Kurata, Hakusui, & Tachizawa, ; Yabe et al., ), the total value of dose‐dependent pharmacokinetic parameters of ofloxacin represents twice the correspondent value of LFX. Therefore, a 5 mg/kg dose of ofloxacin corresponds to a 2.5 mg/kg dose of LFX; if, for this dose the AUC of ofloxacin is 34.7 μg hr/ml (Yabe et al., ), half of it (17.35 μg hr/ml) corresponds to a 2.5 mg/kg dose of LFX.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of levofloxacin after single intravenous, oral and subcutaneous administration to dogs

Landoni

Albarellos

2018

Vet Pharm & Therapeutics

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The pharmacokinetic properties of the fluoroquinolone levofloxacin (LFX) were investigated in six dogs after single intravenous, oral and subcutaneous administration at a dose of 2.5, 5 and 5 mg/kg, respectively. After intravenous administration, distribution was rapid (T½dist 0.127 ± 0.055 hr) and wide as reflected by the volume of distribution of 1.20 ± 0.13 L/kg. Drug elimination was relatively slow with a total body clearance of 0.11 ± 0.03 L kg−1 hr−1 and a T½ for this process of 7.85 ± 2.30 hr. After oral and subcutaneous administration, absorption half‐life and Tmax were 0.35 and 0.80 hr and 1.82 and 2.82 hr, respectively. The bioavailability was significantly higher (p ˂ 0.05) after subcutaneous than oral administration (79.90 vs. 60.94%). No statistically significant differences were observed between other pharmacokinetic parameters. Considering the AUC24 hr/MIC and Cmax/MIC ratios obtained, it can be concluded that LFX administered intravenously (2.5 mg/kg), subcutaneously (5 mg/kg) or orally (5 mg/kg) is efficacious against Gram‐negative bacteria with MIC values of 0.1 μg/ml. For Gram‐positive bacteria with MIC values of 0.5 μg/kg, only SC and PO administration at a dosage of 5 mg/kg showed to be efficacious. MIC‐based PK/PD analysis by Monte Carlo simulation indicates that the proposed dose regimens of LFX, 5 and 7.5 mg/kg/24 hr by SC route and 10 mg/kg/24 hr by oral route, in dogs may be adequate to recommend as an empirical therapy against S. aureus strains with MIC ≤ 0.5 μg/ml and E. coli strains with MIC values ≤0.125 μg/ml.

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“…Renal tubular secretion is mediated by active transport systems specific for acids and bases. Species similarities (24,64) and differences (24,47,57,58) in renal secretion have been found to exist. Renal tubular reabsorption is the third component of renal excretion and can be either an active or passive process.…”

Section: Rate Of Filtrationmentioning

confidence: 99%

Issues Related to the Use of Canines in Toxicologic Pathology—Issues With Pharmacokinetics and Metabolism

Tibbitts

2003

Toxicol Pathol

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The dog is a commonly used animal model by virtue of its size, well-characterized physiology, and ease of handling. For these reasons and others, dogs are also useful in pharmacokinetic and metabolism studies during the development of both human and veterinary pharmaceutical products. In comparison with humans, or with other animals, dogs have some unique physiologic attributes that can affect the disposition of drugs. Species differences in gastrointestinal physiology, metabolism, renal function, and protein binding can affect the correlation of the pharmacokinetics and toxicology of dogs with those of other species. With the use of relevant examples, this article will provide an introduction to characteristics of dog physiology and their impact on pharmacokinetics, metabolism, drug disposition, toxicity, and dose selection.

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Species-related stereoselective disposition of ofloxacin in the rat, dog and monkey

Cited by 21 publications

References 22 publications

HPLC separation and quantification of ofloxacin enantiomers in rabbit plasma. Application to pharmacokinetic studies

HPLC separation and quantification of ofloxacin enantiomers in rabbit plasma. Application to pharmacokinetic studies

Pharmacokinetics of levofloxacin after single intravenous, oral and subcutaneous administration to dogs

Issues Related to the Use of Canines in Toxicologic Pathology—Issues With Pharmacokinetics and Metabolism

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