Pharmacological aspects of chloramphenicol administration by the intramammary route to lactating dairy cows

Abstract

SUMMARYConcentrations of chloramphenicol (CM) were determined, by microbiological assay, in the milk and blood serum of 17 culled dairy cows after intramammary infusion of an approved parenteral CM product (Gloveticol®) and in the milk of 16 lactating cows after treatment with two approved CM products for intramammary infusion, at dosages ranging from 1 to 30 gl cow. CM was quickly absorbed from the udder into the blood circulation; the doses of 12.5 and 25 glcow were almost completely absorbed within 20 hours. Absorption half-life (t1/2ab) from fully functioning quarters was 57±18 minutes, and the t1/2ab from partially functioning quarters was 125±37 minutes. Mean peak serum CM concentrations were 6.1, 16.2, and 37.4 mg 1 ml after the cows had been infused with 5, 12.5, and 25 g, respectively. These values were considerably higher than the corresponding peak serum CM concentrations reported following intramuscular injection of equivalent doses of the drug. CM residues were not detectible microbiologically in milk from treated quarters 20 hours after treatment with 5 g or 6.25 g, and 36 hours after treatment with 15 g. Drug concentrations in the milk from the non-treated quarters were approximately 70 per cent of the corresponding serum drug levels.Serum CM concentrations of potential therapeutic value in the treatment of gram-negative bacterial infections, i.e. > 5 mg/ ml, were maintained for 8 hours after cows had been infused with 12.5 g, and for 12 hours after infusion with 25 g.The implications of the improved 'systemic availability of CM infused by the intramammary route over the intramuscular route are discussed in terms of potential therapeutic efficacy, local irritation, and duration of drug residues.

Scientific Opinion on Chloramphenicol in food and feed

“…It was concluded that the overall absorption from the injection site was relatively poor. Therefore, Nouws and Ziv (1982) performed a study with intramammary infusion of different dosages of chloramphenicol (5, 12.5 and 25 g) using dairy cows of 475-525 kg. This resulted in a dose-related increase in serum levels with maximum levels of 6, 16 and 37 µg/mL, respectively, as determined with the microbiological assay.…”

Pharmacokinetic, residue and irritation aspects of chloramphenicol sodium succinate and a chloramphenicol base formulation following intramuscular administration to ruminants

“…In the final elimination phase of CAP formulations, some other metabolites have been detected in low concentrations in the urine of cows, but not in edible tissues, and no accumulation of CAP or its metabolites was shown in edible tissues (10). CAP as well as its metabolites are eliminated completely from the body following intramammary or intravenous administration of chloramphenicol base to dairy cows (5,10,16).…”

“…lung, udder) (11,12,16,20,21). The main metabolite of CAP in dairy cows is its glucuronide (10,12,16). In the final elimination phase of CAP formulations, some other metabolites have been detected in low concentrations in the urine of cows, but not in edible tissues, and no accumulation of CAP or its metabolites was shown in edible tissues (10).…”

“…After slaughter, the CAP residues left in liver and kidney are reduced largely to a microbiologically inactive arylamine, which can be detected with the Bratton & Marshall diazo coupling reagents (13,16). With respect to potential public health hazards on ingestion of CAP residues a tolerance level of 10-50 ng/g tissue has been proposed (3,7,12 …”

“…Besides the broad-spectrum activity its possesses also favourable physico-chemical properties: it is a lipophilic drug with ready intracellular penetration as well as that of the intercellular spaces, the central nervous system, and the aqueous humor; furthermore it rapidly passes epithelial membranes (e.g. lung, udder) (11,12,16,20,21). The main metabolite of CAP in dairy cows is its glucuronide (10,12,16).…”