C14.3 Concentrations in plasma and urinary excretion of ciprofloxacin XR (1,000 milligrams) versus those of levofloxacin (500 milligrams) in healthy volunteers receiving a single oral dose

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Concentrations in Plasma and Urinary Excretion of Ciprofloxaein X R (1,000 Milligrams) versus those of Levofloxacin (500 Milligrams) in Healthy Volunteers Receiving a Single Oral Dose Florian M.E. WAGENLEHNER l, Uwe TISCHMEYER l, Martina KINZIG SCHIPPERS 2, Christine WAGENLEHNER 1, Fritz SORGEL 2, Kurt G. NABER 1. 1St. Elisabeth Hospital, Straubing,

Germany; Institute for Biomedical arm Pharmaceutical Research (IBMP), Nit'rnberg-Heroldsberg, Germany Objective: To compare tile plasma and urine concentrations of ciprofloxacin XR and its pharmacokinetic parameters with those of levofloxacin (LVX) Significance: The new extended release formulation of ciprofloxacin (Cipro XR) was designed for once daily administration in the treatment of urinary tract infection (UTI). Study Design: Rmldomized crossover study Population: Healthy volunteeiz Methodology: In a randomized crossover study, 12 volunteers (]6 males, 6 females) received a single opal dose of 1000mg of Cipro XR or 500mg of LVX to assess the concentrations (by high pressure liquid chromatography) in plasma and tile urinary excretion at intervals up to 36h. Tile foUowing pharmacokinetic parameters were studied: Cmax, tmax, tl/2, AUC, Cltot, Cli'en, Vd~, Vdss, maximal urinary concentration (Umax), and urinary excretion (LIE). Results: Both fluoroquinolones were tolerated well. The mean phar macokinetic parameters are shown in the table. The median cumulative levels of renal excretion of the administered dose of the parent drag were 43% for ciprofloxacin (range, 14 to 51%; mean + standard deviation, 41% + 10%), mid 80% for levofloxacin (range, 74 to 88%; mean + standard deviation, 80% + 5%). Cmax tmax tl/2 AUC C l t o t C k e n Vdp (glmL) h h (g,h/mL) mLhnin mLhnin L

Vdss Umax UE L (glmL) %

CiproXR 3.28* 1.96" 8.17 19.5" 927.1" 351.3" 856.4* 485.9* 890~.5* 43* LVX 6.17" 1.16" 6.40 47.8* 174.4" 142.9" 97.0* 95.5* 498.9* 80* • t4est (P<0.05) Cmax, AUC, and UE were statistically significant liigher in tile LVX phase, whereas ttle other phamlacokinetic indices, except t l ~ , were statistically significantly higher in the cipro XR phase. Conclusion: After oral administration of Cipro XR 1000 mg and LVX 500 mg, Cmax and AUC in plasma were significantly higher in the LVX phase. The lenal excretion (in mg) of cipro XR 1000mg once daily, however, is equivalent to that of LVX 500 mg and overall coropmable urinary concentrations and areas under ttle urinary concentrations are reached by both drags. Therefore, it can he assumed that the two doses investigated can be considered equivalent for the treatment of UTI.

C14.4

Concentrations in Plasma, Urinary Excretion, and Bactericidal Activity of Levofloxaein (500) versus those of Ciprofloxacin (500 Milligrams) in Healthy Volunteers Receiving a Single Oral Dose Florian M.E. WAGENLEHNER l, Chriatoph K. NABER 2, Martina KINZIG SCHIPPERS B, Fritz SORGEL B, Kurt G. NABER 1. 1St.

Elisabeth Hospital, Straubing, Germany; 2Universi~ of Essen, Germany; 3(IBMP), Ni~'rnberg-Heroldsberg, Germany Objectives: To assess the concentrations of ciprofloxacin (1500 mg) and levofloxacin (500 mg) after a single oral dose in plasma (up to 24 ill), urinary excretion and bactericidal titers in urine (LIBT) at intervals up to 120h Significance: Therapy and dosing in complicated urinary tract infec tions

Study Design: Randomized crossover study Population: 14 volunteers (7 males, 7 females) Methodology: In a randomized crossover study, 14 volunteers (7 males, 7 females) received a single oral dose of 500mg of levofloxacin or 500mg of ciprofloxacin to assess the concentrations by bigh-plessuie liquid chromatography in plasma (up to 24 Ill), urinary excretion and bactericidal titers in urine (UBT) at intervals up to 120h. Results: The mean (median) maximum concentration of levofloxacin in plasma was 6.1 (16.1) mg/liter, and that of ciprofloxacin 2.2 (2.31) mg/liter. The median (range; mean -c standard deviation) cumulative levels of renal excretion of the administeied dose of ttle parent dlaag were 81.2% (69.6 to 86.7%; 81.2% 4_ 5.2%) for levofloxacin and 36.2% (25.9 to 50.3%; 37.2% ± 8.1%) for ciprofloxacin. The UBTs, i.e. ttle liigtlest dilution in powers of two (with antibiotic free urine used as the diluent) of urine that was still bactericidal, were determined for a reference strain and nine clinical uropathogens for which the MICs of levofloxacin and ciprofloxacin were as follows: Escherichia coli ATCC 25922, 0.03 and 0.008 mgflitel; respectively; Escherichia coli (nalidixic acid resistant), 0.25 and 0.125 mgfliter, respectively; Klebsiella pneumoniae, 0.03 and 0.008 mg/liter, respectively; Proteus mirabilis, 0.06 and 0.03 mg/liter, respectively; Pseudomonas aeruginosa, 2 and 0.5 mg/liter, respectively; Staphylococcus aureus (fluoroquinolone susceptible), 2 and 4 mg/liter, respectively; Staphylococcus aureus (fluoroquinolone-resistmrt), 8 and 32 mgfliter, respectively; Staphylococcus saprophyticus, 0.25 and 0.25 mg/litei, iespectively; Enterococcus faecalis (fluoroquinolonesusceptible), 1 and 1 mgfliter, iespectively; and Enterococcusfaecalis (flum'oquinoloneresiatant), 16 and 32 mg/liter, respectively. The median UBTs of both quinolones measured within the first 12 h were between 0 (no bactericidal activity of undiluted urine) and 1: 1024, correlating with the MICs of ttle strains. For Gram-negative strains ttle UBTs of both quinolones were coroparable, despite tile lower MICs of ciprofloxacin. During further time course, however, the UBTs of levofloxacin were significmrtly liigher than those of ciprofloxacin. For Gram positive strains, for which the MICs of levofloxacin were equal to or lower than those of ciprofloxacin, the UBTs of levofloxacin were significantly higher already from the beginning. Conclusion: It can he concluded that ovemU, the doses of the tested two fluoroquinolones may be consideied equivalent in tile treatment of complicated urinary tract infection, if for ciprofloxacin a twice daily and for levofloxacin a once daily dosing is recommended.

C14.5 Acute Pyelonephritis in the Renal Graft: A Diagnostic Challenge Giorgina PICCOLI, M. BURDESE, E. MEZZA, V. CONSIGLIO, G. SARGIOTI'O, J. MAASS, M. ROSSETTI, C. GUARENA, G. PICCIOTTO, R SEGOLONI. University of Torino, Italy Objective: To report on five cases of acute graft pyeloneplititis in tile renal graft, diagnosed by means of imaging techniques or kidney biopsy in the absence of tile "classical" clinical picture Significance: Acute pyelonephritis is a common complication of kidney transplantation, occurring in up to 1% of the grafts. Diagnosis is mainly clinical; atypical presentations are seldom reported. The diagnostic role for imaging techniques is not defined. Study Design: Case series (prospective liistmic al analysis of the clinical charts) Setting: Outpatient care unit satellite of the University of Torino, Italy Population: Patients who received a kidney or a kidney pancreas graft Methodology: Descriptive analysis of the clinical charts Results; Five cases of acute graft pyeloneplnitis are reported (13kidney, 2 pancreas-kidney grafts): 3 females, 2 males, with a median age 48 years and a post-trmlsplant foUow-up of 2.8 months. Predisposing factors included diabetes in three, and enteric bladder in one case. None presented the "classic" clinical diagnostic tetrad of fever, positive urine cultures, lower urinary tract symptoms, and serum creatinine increase. At diagnosis, fever occurred in two of tile five cases, cieatinine increase in one, positive