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

Abstract

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.

Pharmacokinetic profiles of levofloxacin after intravenous, intramuscular and subcutaneous administration to rabbits (Oryctolagus cuniculus)

“…Although extraction ratio values were not computed in other species in which levofloxacin PKs were established, we calculated approximate extraction ratios for the above-mentioned studies. Low levofloxacin extraction ratios were predicted in cats, dogs, and rabbits (around 2%) based on the clearance and mean animal body weights reported by Albarellos et al [10], Landoni and Albarellos [7], Madsen et al [11] and Destache et al [21]. In food-producing animals, the levofloxacin extraction rate is also low.…”

“…Therefore, understanding of drug kinetics and efficacy from experimental modeling of as-yet unapproved drugs for animal use can contribute to the potential use of these drugs in the future. At present, levofloxacin is approved for veterinary use in some countries [7] and might be used in other countries where antimicrobial agent use is not regulated/controlled by local laws. Regardless, the authors do not endorse the extra-label use of levofloxacin; instead, we undertook this study to investigate the potential use of levofloxacin in rabbits as a basis for further research.…”

“…Levofloxacin, a third-generation fluoroquinolone, is active against a wide range of Grampositive and Gram-negative microorganisms and has improved activity, compared to older fluoroquinolones, against streptococci and anaerobes [6,8,9]. The pharmacokinetics (PKs) of levofloxacin has already been established in several domesticated mammalian pets [7,10,11], non-pets [12][13][14], and birds [15][16][17][18]. Moreover, there are several research papers published in recent years that show increased interest in levofloxacin having potential application as an off-label drug for some pet animals (dogs).…”

“…Moreover, there are several research papers published in recent years that show increased interest in levofloxacin having potential application as an off-label drug for some pet animals (dogs). Pharmacokinetic/ pharmacodynamic (PK/PD) indices of fluoroquinolones indicate the effectiveness of this class of drugs [19,20], and they imply that levofloxacin has promise in the treatment of infections in animals [7,11].…”

Pharmacokinetics of levofloxacin mesylate in healthy adult giant panda after single‐dose administration via different routes

“…Levofloxacin is the mesylate monohydrate of levofloxacin used to treat infections (Hou et al., 1999). Levofloxacin has promise in the treatment of infections in animals (Davis & Bryson, 1994; Landoni & Albarellos, 2019). The pharmacokinetics of levofloxacin has already been established in several animals, such as dogs (Landoni & Albarellos, 2019; Madsen et al., 2019), cats (Albarellos et al., 2005), camels (Goudah, 2009), goats (Goudah & Abo‐El‐Sooud, 2009), broiler chickens (Lee et al., 2017), and rabbits (Sitovs et al., 2020).…”