Urothelial mucosal concentration of levofloxacin administered before transurethral resection: Is the mucosal concentration predictable?
BACKGROUND
Although it is an established surgical technique, transurethral resection (TUR) is associated with a certain incidence of postoperative bacteriuria. Assessment was made whether the urothelial mucosal concentration of an antibiotic administered before TUR was high enough to decrease the incidence of urinary tract infection (UTI). Also investigated were factors predicting the organ concentration.


METHODS
Forty-nine patients (45 men and four women aged 51-79 years with a median age of 70 years) who underwent TUR between August 1996 and September 1997 were enrolled in the study. Each patient received 200 mg of levofloxacin (LVFX) about two hours before surgery. Blood and bladder urine were collected and urothelial mucosa was harvested at the time of TUR. Then the LVFX concentration in these samples was measured using high-performance liquid chromatography. The association between drug levels, or the ratio to the serum concentration, and factors likely to affect the vascular system that delivers the drug (age, bodyweight, blood pressure, pulse rate, total cholesterol and diabetes mellitus) were investigated.


RESULTS
The mean serum drug level was 2.4 microg/mL, and it was 206.4 microg/mL in the urine and 5.7 microg/mL in the urothelial mucosa. The mean ratio of the mucosal to serum concentrations was 2.6. The urinary drug concentration showed no association with any of the factors assessed, while the serum concentration decreased with increasing bodyweight (P = 0.03). As the diastolic blood pressure increased, both the mucosal drug concentration and the mucosa/serum ratio decreased (P < 0.01). When the relationship between the serum and mucosal concentrations was investigated, no correlation was found. However, the mucosa/serum ratio (indicating the transfer of LVFX from the blood) was positively correlated with the mucosal concentration.


CONCLUSIONS
Preoperative administration of LVFX was demonstrated to have potential value for the prophylaxis of UTI after TUR. Both the mucosal concentration and the mucosa/serum ratio were correlated with the diastolic blood pressure. As the diastolic blood pressure seems to be an indicator of the tissue concentration of LVFX, it may be possible to set the optimum dose based on the diastolic pressure.
Department of Urology, Ebina General Hospital, Kanagawa, Nippon Medical School, Tokyo, Japan. tomohatt@da2.so-net.ne.jp
T
T
Hattori
G
G
Kimura
Y
Y
Kondo
K
K
Horiuchi
N
N
Tsuboi
K
K
Yoshida
M
M
Akimoto
D000368:Aged; D000892:Anti-Infective Agents, Urinary / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D015242:Ofloxacin / Q000493:pharmacokinetics*; D011300:Preoperative Care; D014018:Tissue Distribution; D014521:Urethra; D019459:Urothelium / Q000378:metabolism*
D000892:Anti-Infective Agents, Urinary; D064704:Levofloxacin; D015242:Ofloxacin