Angioplasty increases target site concentrations of ciprofloxacin in patients with peripheral arterial occlusive disease.
OBJECTIVE
Patients with peripheral arterial occlusive disease are prone to soft tissue infections and frequently require antibiotics. To date, however, it is not known whether improvement of arterial blood flow by angioplasty of stenosis increases antibiotic concentrations in ischemic lesions.


METHODS
All patients were scheduled to undergo elective percutaneous transluminal angioplasty (n = 10). Following a single, 400-mg dose of ciprofloxacin, drug concentrations in plasma, ischemic and healthy soft tissue; arterial peak systolic velocity; and ankle-brachial pressure index were assessed before and after angioplasty. Unbound ciprofloxacin concentrations were measured at the site of infection with use of in vivo microdialysis.


RESULTS
Angioplasty increased peak systolic velocity and ankle-brachial pressure index compared with baseline (P <.002). Before angioplasty area under concentration-time curve (AUC(0-300)) values for ciprofloxacin were lower in ischemic tissue than in healthy tissue, with median values of 7.1 mg.h/L (range, 3.5-13.0) and 11.3 mg.h/L (range, 3.4-19.0), respectively (P =.03). After angioplasty AUC(0-300) values were identical in ischemic and healthy adipose tissue; median AUC(0-300) values were 8.0 mg.h/L (range, 4.0-20.7) and 8.5 mg.h/L (range, 4.4-22.9), respectively (P =.7). A combined in vivo pharmacokinetic/in vitro pharmacodynamic simulation based on tissue concentration data indicates that this difference in pharmacokinetics is also reflected in antimicrobial effect.


CONCLUSIONS
Antibiotic concentrations are reduced significantly in ischemic lesions compared to those of healthy adipose tissue in patients with peripheral arterial occlusive disease. From the present data it might be speculated that improvement of arterial blood flow at the affected extremity is associated with increased cure rates of soft tissue infections in these patients.
Joukhadar
C
C
Division of Clinical Pharmacokinetics, Department of Clinical Pharmacology, University of Vienna Medical School, Vienna, Austria.
Klein
N
N
Frossard
M
M
Minar
E
E
Stass
H
H
Lackner
E
E
Herrmann
M
M
Riedmüller
E
E
Müller
M
M
D000273:Adipose Tissue / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D017130:Angioplasty; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001157:Arterial Occlusive Diseases / Q000378:metabolism* / Q000601:surgery; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007511:Ischemia / Q000378:metabolism; D008297:Male; D008826:Microbial Sensitivity Tests; D017551:Microdialysis; D008875:Middle Aged; D014656:Vascular Surgical Procedures
D000890:Anti-Infective Agents; D002939:Ciprofloxacin