Pharmacotherapeutic group: Antibacterial for systemic use, first-generation cephalosporins
ATCvet Code: QJ01DB01
Pharmacodynamic properties
The mechanism of action of cephalosporins resembles that of the penicillins, in particular that of ampicillin (common beta-lactam ring). Cephalosporins especially has a time-dependent bactericidal effect in dividing bacteria. They bind irreversibly with 'penicillin-binding proteins (PBPs’), enzymes that are needed for the cross-coupling of peptidoglycan strands during the synthesis of the bacterial cell wall. This interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell strength and rigidity, and results in abnormal cell growth and cell lysis. Cephalexin is active against both gram positive and some gram negative bacteria.
The following CLSI cephalothin veterinary breakpoints are available for dogs (CLSI VET01S ed. 5, November 2020).
Cephalothin can be used as indicator of first generation cephalosporins.
Bacterial species | Susceptible | Resistant |
Skin and soft tissue infections: | | |
Staphylococcus aureus and Staphylococcus pseudintermedius | ≤ 2 μg/m | ≥ 4 μg/ml |
Streptococcus spp. and E. coli | ≤ 2 μg/ml | ≥ 8 μg/ml |
Urinary tract infections: | | |
E. coli, Klebsiella pneumoniae and Proteus mirabilis | ≤ 16 μg/ml | ≥ 32 μg/ml |
As with penicillins resistance to cefalexin may be due to one of the following mechanisms of resistance: the production of various beta-lactamases, encoded on plasmids or not encoded or by multistage mutations. In the first case, there is almost always cross-resistance with ampicillin; in the other cases there is partial or complete cross-resistance to all penicillins and cephalosporins. Conversely, methicillin-resistant staphylococci are unsusceptible to cephalosporins.
Pharmacokinetic properties
After administration of cephalexin monohydrate cephalexin rapidly and almost completely absorbed in the gastrointestinal tract. Absorption is delayed by food (lower blood levels). Protein plasma binding is approximately 20%.
Single oral administration of 20 mg of cephalexin per kg body weight to dogs resulted in a Tmax of approximately 1-1.5 hours, a Cmax in plasma of about 15 µg/ml and an elimination half-life of about 2 hours (bioavailability = 75-80%). The volume of distribution is 1.62 l/kg.
Single oral administration of 15 mg cefalexin per kg body weight to cats gave a Tmax of approximately 1.5-2 hours, a Cmax in plasma of about 20 µg/ml and an elimination half-life of approximately 2 hours (bioavailability = 56%). The volume of distribution is 0.83 l/kg.
After absorption, cephalexin is well distributed in the extracellular fluids of the body, however, the passage of biological membranes is limited. The concentrations of cephalexin are highest in the kidneys (urine), and bile, followed by the liver, lungs, heart, skeletal muscle and spleen.
Hardly any metabolism occurs in the liver. Elimination is almost entirely via the kidneys by tubular excretion and glomerular filtration. Cephalexin is also excreted in the bile in a concentration that is equal or somewhat higher than in the blood.