Imipenem pharmacokinetics in elective colorectal surgery

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Surgical Infectious Diseases

Background:

• Antibiotic prophylaxis is crucial in colorectal surgery to prevent surgical site infections.
• Understanding drug distribution and elimination is essential for optimizing prophylactic regimens.

Purpose of the Study:

• To investigate the pharmacokinetics of imipenem when co-administered with cilastatin in patients undergoing elective colorectal surgery.
• To determine imipenem concentrations in plasma and various tissues (fat, muscle, viscera) over time.
• To assess if achieved drug levels are sufficient to inhibit common pathogens during surgery.

Main Methods:

• Intravenous administration of 1g imipenem and 1g cilastatin to 22 patients.
• Collection of plasma, fat, muscle, and visceral samples at multiple time points post-injection.
• Assay of imipenem concentrations using validated analytical methods.

Main Results:

• Plasma imipenem concentrations were approximately tenfold higher than tissue concentrations.
• Imipenem exhibited a similar half-life of approximately 1 hour in plasma, muscle, and fat.
• Visceral tissue showed a slower elimination with a half-life of 83 minutes.
• Therapeutic imipenem levels, exceeding the MIC90 for common pathogens, were maintained for at least the initial two hours of surgery.

Conclusions:

• Imipenem, when given with cilastatin, achieves adequate plasma and tissue concentrations for antibiotic prophylaxis in colorectal surgery.
• The pharmacokinetic profile supports the use of imipenem as a suitable prophylactic agent in this surgical setting.