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.

Highlights

  • The administration of drugs with therapeutic purposes must be done selecting a dosage regimen both effective and safe

  • 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

  • For the anti-infective therapy, a close relationship between plasma concentrations and antibacterial activity of the chosen antibiotic has been previously demonstrated by PK/PD modelling, and the optimal dosage regimen has been determined for several antibiotics and species using a surrogate index of clinical outcome; that is, for beta-lactam antibiotics, the time for which plasma concentrations is above the minimum inhibitory concentration (MIC) of the invading pathogen (T > MIC) [1]

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Summary

Introduction

The administration of drugs with therapeutic purposes must be done selecting a dosage regimen both effective and safe. For the anti-infective therapy, a close relationship between plasma concentrations and antibacterial activity of the chosen antibiotic has been previously demonstrated by PK/PD modelling, and the optimal dosage regimen has been determined for several antibiotics and species using a surrogate index of clinical outcome; that is, for beta-lactam antibiotics, the time for which plasma concentrations is above the minimum inhibitory concentration (MIC) of the invading pathogen (T > MIC) [1]. Pharmacokinetic and MIC data about South American camelids as llamas (Lama glama) are scarce, and veterinarians estimate the dosage regimen based on information obtained from other species, usually ruminants. This extrapolation may result in ineffective therapies, mainly due to the unique interspecies pharmacokinetic differences in drug transport across membranes, protein binding, and drug metabolism and excretion [1].

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