Azlocillin and cefonicid penetration into bone enhanced by probenecid

Area of Science:

• Pharmacology
• Orthopedic Surgery
• Infectious Diseases

Background:

• Antibiotic penetration into bone is crucial for treating orthopedic infections.
• Azlocillin and cefonicid are commonly used antibiotics.
• Probenecid is known to affect renal tubular secretion of various drugs.

Purpose of the Study:

• To evaluate the penetration of azlocillin and cefonicid into rabbit humerus and scapula.
• To determine the effect of probenecid on antibiotic concentrations in serum and bone.
• To assess the impact of probenecid on the pharmacokinetic profile of these antibiotics in bone tissue.

Main Methods:

• Administration of azlocillin (IV) or cefonicid (IM) to rabbits.
• Concurrent administration or pretreatment with probenecid.
• Measurement of antibiotic concentrations in serum and bone (humerus, scapula) over time using validated assays.
• Pharmacokinetic analysis including peak levels, half-life, and duration of detectable concentrations.

Main Results:

• Probenecid significantly increased serum and bone concentrations of both azlocillin and cefonicid.
• Azlocillin bone levels increased from 2.7/7.1 µg/g to 3.9/11.7 µg/g (humerus/scapula).
• Cefonicid bone levels increased from 0.66/1.8 µg/g to 1.7/2.8 µg/g (humerus/scapula).
• Probenecid prolonged the serum half-life of azlocillin (0.44 to 0.65 h) and cefonicid (1.4 to 2.94 h).
• Detectable antibiotic levels persisted longer in bone with probenecid pretreatment.

Conclusions:

• Concomitant administration of probenecid significantly enhances the penetration and retention of azlocillin and cefonicid in rabbit bone.
• Probenecid alters the pharmacokinetics of these antibiotics, leading to higher bone concentrations.
• These findings suggest a potential adjunctive role for probenecid in antibiotic therapy for bone infections.