Penetration of ofloxacin into heart valves, myocardium, mediastinal fat, and sternal bone marrow in humans.
Ofloxacin penetration into heart tissue (valve and myocardium), mediastinal fat, and sternal bone marrow was the object of a prospective nonrandomized study. Thirty-six patients undergoing mitral and/or aortic valve replacement were included. Patients were divided into two groups of 18 patients each. Group 1 patients were administered a single 400-mg intravenous dose of ofloxacin over a 30-min period upon anesthesia (n = 6) or at 1 h (n = 6) or 6 h (n = 6) prior to surgery. Group 2 patients received a 200-mg oral dose of ofloxacin every 12 h during the 48 h preceding surgery. In this group, the final dose of ofloxacin was administered 3 h (n = 9) or 8 h (n = 9) before anesthesia. Plasma and tissue ofloxacin concentrations were assayed by high-pressure liquid chromatography. In group 1 patients, the peak level in plasma was 15.9 +/- 2.5 micrograms/ml. Peak ofloxacin levels in tissue were reached by hour 1 and were 8.89 +/- 2.16 micrograms/g in myocardium and 5 +/- 0.75 micrograms/g in heart valves. A significant decrease in ofloxacin levels in heart valve tissue and sternal bone marrow was observed after hour 3. Nevertheless, ofloxacin myocardial, heart valve, and sternal bone marrow levels remained higher than the MICs for the usually susceptible pathogens for at least 3 h. In group 2 patients, myocardial levels were long lasting (6.46 +/- 1.92 micrograms/g [4 to 8 h] and 5.92 +/- 0.95 micrograms/g [8 to 12 h]) and remained higher than those observed in the other tissues over the entire study period. A progressive but insignificant decrease in ofloxacin heart valve levels was observed (from 2.46 +/- 0.40 micrograms/g [4 to 8 h] to 1.57 +/- 0.22 micrograms/g [8 to 12 h]). In both groups, concentration in mediastinal fat were lower and tended to decrease with time. These were 1.83 +/- 0.61 micrograms/g with the first hour and 0.85 +/- 0.43 micrograms/g between hours 8 and 12 in group 1 and 1.74 +/- 0.52 micrograms/g between hours 4 and 8 and 0.67 +/- 0.11 micrograms/g between hours 8 and 12 in group 2. In conclusion, satisfactory diffusion of ofloxacin into heart tissue seems to favor use of the drug in the treatment of bacterial endocarditis due to susceptible pathogens. Furthermore, the progressively decreasing concentrations observed in heart valve and sternal bone marrow and the poor levels achieved in mediastinal fat suggest the need for renewing injection 3 h following initial infusion if the drug is used as an antibiotic prophylactic agent during cardiovascular surgery.
Mertes
P M
PM
Laboratoire de Physiologie, CHU de Brabois, Vandoeuvre, France.
Jehl
F
F
Burtin
P
P
Dopff
C
C
Pinelli
G
G
Villemot
J P
JP
Monteil
H
H
Dureux
J B
JB
D000273:Adipose Tissue / Q000378:metabolism*; D000284:Administration, Oral; D000368:Aged; D001021:Aortic Valve / Q000378:metabolism / Q000601:surgery; D001853:Bone Marrow / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D006350:Heart Valve Prosthesis; D006351:Heart Valves / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008482:Mediastinum; D008875:Middle Aged; D008943:Mitral Valve / Q000378:metabolism / Q000601:surgery; D009206:Myocardium / Q000378:metabolism*; D015242:Ofloxacin / Q000097:blood / Q000493:pharmacokinetics*; D011446:Prospective Studies; D013249:Sternum
D015242:Ofloxacin