Single- and multiple-dose pharmacokinetics of intravenous moxifloxacin in patients with severe hepatic impairment.
OBJECTIVE
The aim of this study was to investigate the single- and multiple-dose pharmacokinetics (PK) of moxifloxacin and its penetration into ascitic fluid in patients with severe liver insufficiency (Child-Pugh class C).


METHODS
In a single-centre, prospective, open-label study, nine adult cirrhosis patients were treated with 400 mg moxifloxacin infusion once a day. On days 1 and 3, drug concentrations in serum and ascites were determined before and at different time points up to 24 h after medication with a validated HPLC method.


RESULTS
On day 1, serum concentrations of moxifloxacin decreased from a median of 3.7 mg/L at 1 h to 0.6 mg/L at 24 h. On day 3, serum peak and trough levels were only moderately increased in comparison with day 1, with moxifloxacin concentrations of 3.9 mg/L after 1 h and 0.6 mg/L 24 h after the third infusion. The AUC values were also slightly, but not statistically significantly, increased on day 3. Calculations of t(1/2), mean residence time, CL(tot) and V(ss) revealed no significant differences between days 1 and 3. Median concentrations of moxifloxacin in ascitic fluid were 1.4 mg/L (3 h after infusion) and 1.3 mg/L (6 h) on day 1 and 2.1 mg/L (3 h) and 1.9 mg/L (6 h) on day 3. Median ascites/serum ratios did not vary between days 1 and 3.


CONCLUSIONS
PK parameters of moxifloxacin in patients with advanced liver cirrhosis differed only marginally from those from healthy control groups given in the literature. After multiple dosing, no drug accumulation was seen. Therefore, we conclude that a dose adjustment is not necessary in this patient group. Ascitic fluid reached bactericidal levels for common bacteria found in spontaneous bacterial peritonitis.
Barth
Jürgen
J
Department of Internal Medicine, BG Clinic Bergmannstrost, Halle/Saale, Germany. juergen.barth@bergmannstrost.com
Jäger
Doris
D
Mundkowski
Ralf
R
Drewelow
Bernd
B
Welte
Tobias
T
Burkhardt
Olaf
O
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001202:Ascitic Fluid / Q000737:chemistry; D001372:Aza Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D024841:Fluoroquinolones; D006207:Half-Life; D048550:Hepatic Insufficiency; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011446:Prospective Studies; D011804:Quinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D044967:Serum / Q000737:chemistry; D013997:Time Factors
D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin