Penetration kinetics of moxifloxacin in human pancreas: comparison of intravenous vs oral administration

Abstract number: 1134_02_303

Wacke R., Förster S., Park S., Mundkowski R.G., Adam U., Schareck W., Klar E., Drewelow B.

Objectives:

Acute necrotizing pancreatitis is still related to a high mortality rate, based on local infectious complications, particularly due to bacterial infections of the necrotic pancreatic and parapancreatic areas. Limited penetration of antimicrobial drugs in these areas/compartments is considered to be a major cause of failure of therapy of severe local pancreatic infections. However, fluoroquinolones (e.g. ciprofloxacin, levofloxacin) have been shown to penetrate sufficiently into pancreatic tissue. On that score, the value of new quinolones such as moxifloxacin (MXF) has not been investigated yet. Using a rat model of acute necrotizing pancreatitis MXF has been demonstrated to penetrate rapidly and efficiently into pancreatic tissue, also into the inflamed and necrotic pancreas.

Methods:

Addressing the penetration capability of MXF following intravenous (IV) or oral (PO) administration with respect to the human pancreas, a prospective clinical trial was designed using a single IV (20 patients) or PO dose (40 patients) of 400 mg MXF for antimicrobial prophylaxis in patients undergoing pancreas resection. Samples were taken from blood and from resection area of pancreatic tissue at two time points after application (1st sample at the beginning, 2nd sample at the end of resection). Concentrations of MXF were determined by HPLC/UV using ofloxacin as internal standard.

Results:

Mean plasma concentrations of MXF IV and PO at first sampling time (3 - 3.7 h) were 1.8 ± 0.5 and 1.2 ± 0.6 mg/ml, respectively. At the end of resection (4.3–5.3 h) 1.5 ± 0.4 and 1.0 ± 0.5 mg/ml were measured. Corresponding mean concentrations of MXF in pancreatic tissue were 2 to 3times higher (3.1 ± 0.9 and 2.7 ± 1.4 mg/g 1st sample; 3.6 ± 1.5 and 3.1 ± 1.8 mg/g 2nd sample). The MXF concentrations in pancreatic tissue exceeded the MIC90 s of the relevant pathogens encompassed by MXF (e.g. E. coli 0.008–0.06 mg/ml, Klebsiella spp. 0.13 mg/ml, and S. aureus 0.06– 0.12 mg/ml) for at least five hours at the dosing interval.

Conclusion:

MXF has been demonstrated to penetrate efficiently into human pancreatic tissue following IV as well as PO administration. In this study MXF concentrations after PO administration were found to be slightly lower than those observed in healthy subjects probably due to diminished or delayed intestinal absorption prior and during surgery.