Pharmacokinetics of multiple doses of chloramphenicol in fed adult horses.

This research study investigates the effectiveness of the currently recommended dosage of chloramphenicol, an antibiotic, in horses. The findings suggest that the dose isn’t capable of reaching the antimicrobial susceptibility breakpoint in adult horses, indicating a need to reconsider both the dosage and the established breakpoint.

Research Background and Aim

• The research forms part of an ongoing quest to ascertain the impact of the oral administration of chloramphenicol at a dosage of 50 mg/kg (every six hours) in horses.
• The antimicrobial susceptibility breakpoint—the concentration of antibiotic expected to inhibit bacterial growth—for chloramphenicol stands at 8.0 μg/mL. The study explores whether the noted dose can attain this breakpoint in adult horses.
• The studies on this topic were lacking, prompting the researchers to hypothesize that the existing dosage might fail to reach the antimicrobial susceptibility breakpoint.

Research Methods and Process

• The study involved seven adult horses in good health. They were given chloramphenicol at the defined rate repeatedly over a period of four days.
• The researchers drew blood samples from the horses repeatedly over the course of the first 15 doses—specifically at four and six hours following administration of the medication.
• After the 16th dose onward, using a catheter, the participants’ blood was collected at regular time intervals to enable an in-depth pharmacokinetic analysis. This process involves studying how a drug moves within a biological system and how it’s absorbed, distributed, metabolized, and excreted.

Research Findings

• The study’s findings showed that the maximum concentration of chloramphenicol in the participants’ bloodstreams was inconsistent among the horses and ranged between 2.1–42.7 μg/mL.
• The average highest concentration of the drug barely missed the susceptibility breakpoint at 7.7 μg/mL, while the lowest average was significantly lower at 1.5 μg/mL.
• The researchers found that, on average, the drug’s concentration remained above 8.0 μg/mL for only 75 minutes—this is far shorter than the recommended span that is 50% of the dosing interval.
• In a steady state, it was found that the highest achievable concentration of chloramphenicol for at least half of the dosing interval was only 2.0 μg/mL when administered at the dosage specified in the study.

Conclusion

• Therefore, the research suggests that when the medication is given at the frequently recommended dosage, the blood concentration of chloramphenicol doesn’t reach the established susceptibility breakpoint of 8.0 μg/mL in adult horses.
• The authors conclude that the findings call for a reassessment of the standard dosage and established breakpoint of chloramphenicol necessary to effectively treat bacterial infections in adult horses.