Single- and multiple-dose pharmacokinetics of intravenous moxifloxacin in patients with severe hepatic impairment
| Autor: | Ralf G. Mundkowski, Doris Jäger, Olaf Burkhardt, Jürgen Barth, Tobias Welte, Bernd Drewelow |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Serum Microbiology (medical) medicine.medical_specialty Time Factors Cirrhosis Moxifloxacin Gastroenterology Spontaneous bacterial peritonitis Pharmacokinetics Internal medicine Ascites Ascitic Fluid Hepatic Insufficiency Humans Medicine Pharmacology (medical) Prospective Studies Infusions Intravenous Chromatography High Pressure Liquid Aged Antibacterial agent Pharmacology Aza Compounds business.industry Peritoneal fluid Middle Aged medicine.disease Surgery Infectious Diseases Effusion Area Under Curve Quinolines Female medicine.symptom business Fluoroquinolones Half-Life medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 62:575-578 |
| ISSN: | 1460-2091 0305-7453 |
| DOI: | 10.1093/jac/dkn212 |
| Popis: | Objectives 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). Patients and 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. |
| Databáze: | OpenAIRE |
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