Pharmacokinetic study of fibrin clot-ciprofloxacin complex: an in vitro and in vivo experimental investigation.
We prepared a composite of fibrin clot and ciprofloxacin for use as a biodegradable antibiotic delivery system with sustained effect for the treatment of chronic osteomyelitis. In vitro, ten experiments were performed in which 10 mg of ciprofloxacin were incorporated into 4 ml of fibrin clot. The clots were preserved in nutrient broth and incubated at 37 degrees C for a total of 60 days. Every 24 h a broth specimen was obtained, and the ciprofloxacin concentration was determined by microbiological assay. The maximum level of antibiotic was noted on the first day (49.9 +/- 5.1 mg/l). The ciprofloxacin-fibrin clot complexes usually disintegrated after 60 days. In vivo, the fibrin-ciprofloxacin clots were made as previously described. The composite was implanted in the medullary canal of rabbit tibiae, and the antibiotic concentration was measured in bone, muscle, skin and serum. In all tissues around the implant, the concentration of antibiotic exceeded the minimum inhibitory concentration against the common causative organisms of osteomyelitis for 10 days. The implant caused no systemic side-effects, and it is likely to prove clinically useful as a drug delivery system for treating chronic osteomyelitis.
Tsourvakas
S
S
Orthopaedic Department, Laiko General Hospital, Athens, Greece.
Hatzigrigoris
P
P
Tsibinos
A
A
Kanellakopoulou
K
K
Giamarellou
H
H
Dounis
E
E
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001673:Biodegradation, Environmental; D002908:Chronic Disease; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004338:Drug Combinations; D016503:Drug Delivery Systems; D005337:Fibrin / Q000493:pharmacokinetics*; D008826:Microbial Sensitivity Tests; D010019:Osteomyelitis / Q000188:drug therapy; D011817:Rabbits; D014018:Tissue Distribution
D000890:Anti-Infective Agents; D004337:Drug Carriers; D004338:Drug Combinations; D002939:Ciprofloxacin; D005337:Fibrin