Pharmacokinetics of Immediate and Sustained Release Cephalexin Administered by Different Routes to Llamas (Lama glama)

Abstract

We investigate the pharmacokinetics of two different cephalexin formulations administered to llamas by the intravenous (IV), intramuscular (IM), and subcutaneous (SC) routes, the minimum inhibitory concentration (MIC) of cephalexin against some Escherichia coli and staphylococci isolated from llamas, and we apply the PK/PD modelling approach, so that effective dosage recommendations for this species could be made. Six llamas received immediate (10 mg/kg, IV, IM, and SC) and sustained (8 mg/kg IM, SC) release cephalexin. Pharmacokinetic parameters were calculated by noncompartmental approach. Immediate release SC administration produced a significantly longer elimination half-life as compared with the IV and IM administration (1.3 ± 0.2 versus 0.6 ± 0.1 and 0.6 ± 0.1 h, resp.) and higher mean absorption time as compared with the IM administration (1.7 ± 0.5 versus 0.6 ± 0.4 h). Absolute bioavailability was in the range of 72–89% for both formulations and routes of administration. Cephalexin MIC90 values against staphylococci and E. coli were 1.0 and 8.0 μg/mL, respectively. Our results show that the immediate release formulation (10 mg/kg) would be effective for treating staphylococcal infections administered every 8 h (IM) or 12 h (SC), whereas the sustained release formulation (8 mg/kg) would require the IM or SC administration every 12 or 24 h, respectively.

Isolation of Streptococcus agalactiae in a female llama (Lama glama) in South Tyrol (Italy)

“…The determination of MIC was performed in order to evaluate potential antimicrobial resistances. Since no CLSI official breakpoints are available for llamas, and in order to provide a laboratory result, the MIC results (Table 1 ) were evaluated using the bovine clinical breakpoints, even though several authors have observed that llamas, but also other SACs, and bovines present different pharmacokinetics and pharmacodynamics [ 35 , 36 ]. The evaluation, with bovine breakpoints, highlights sensitivity to all antimicrobials tested.…”

Unique Pharmacokinetic and Pharmacodynamic Parameters of Antimicrobials in Goats

“…), respectively. The MIC90 values of cephalexin against coagulase-positive staphylococci and E. coli were 1.0 μg/ml and 8.0 μg/ml, respectively [59]. But MIC90 value (0.01-0.1 μg/ml) of ceftazidime against E. coli, Salmonella species, Pasteurella haemolytica and P. multocida [45] shows that ceftazidime is more active and efficacious than cephalexin, which can be administered 8 mg/kg i.m.…”

“…But MIC90 value (0.01-0.1 μg/ml) of ceftazidime against E. coli, Salmonella species, Pasteurella haemolytica and P. multocida [45] shows that ceftazidime is more active and efficacious than cephalexin, which can be administered 8 mg/kg i.m. or subcut every 12 or 24 h, respectively [59]. Other modes of administration such as ballistic implants and impregnated beads can be employed for some antimicrobials to avoid frequent administration as seen in cefovecin with very long half-life in dogs and cats, allowing a dosing interval of 14 days [60,61].…”

Formulation of Self-Nanoemulsifying Drug Delivery System of Cephalexin: Physiochemical Characterization and Antibacterial Evaluation

“…It is effective in the treatment of Staphylococci and Streptococci infections [2]. It was also found to be effective against Escherichia coli [3]. It is listed as a key access antibiotic in the World Health Organization's essential drug list and it is used as a second choice drug in the form of oral delivery for the effective treatment of chronic obstructive pulmonary disease (COPD), pharyngitis, skin, and soft tissue infections [4].…”

“…To improve solubility, bioavailability, and therapeutic efficacy, several CEP formulations have been developed. The formulations like immediate and sustained release formulations [3], controlled release matrix tablets [8], silica micro-particles [19], non-ionic microemulsions [5], extended-release matrix tablets [7,20], and gastro-floating tablets [6,21] have been developed and tested. The objective of the current research was to develop a CEP SNEDDS and evaluate it by a titration method.…”