Pharmacokinetics of Cefodizime in Patients with Liver Cirrhosis and Ascites

Abstract

The pharmacokinetics of cefodizime were studied in 6 healthy male volunteers (group A) and 6 patients with liver cirrhosis and ascites (group B) receiving 1 g of the drug as an i.v. bolus. Cefodizime was assayed in serum and ascitic fluid (AF) samples by a microbiological assay. The serum concentration-time curve fitted a two-compartment open model in group A and a three-compartment open model in group B. Initially, the serum level of cefodizime in group A exceeded that in group B for about 10 h; thereafter the reverse occurred until 24 h post-dosing. Cefodizime penetrated rapidly into the AF, reaching a peak at 6 h, and its AF level was still above the MIC₉₀ for Ente-robacteriaceae in most patients at 24 h post-dosing. The half-life of distribution did not differ significantly between the two groups, while the elimination half-life was prolonged significantly (p < 0.001) from 2.7 ± 0.2 h in group A to 5.4 ± 0.8 h in group B. The central volume of distribution (V_c) did not differ significantly in the two groups, while the terminal volume of distribution (V_p) was significantly smaller (p < 0.01) in group A (0.172 ± 0.301/kg) than in group B (0.55 ± 0.201/kg). The area under the serum concentration-time curve (AUC_0-∞ serum) was significantly larger (p < 0.001) in group A [322 ± 34 (μg/ ml) • h than in group B (180 ± 34 (μg/ml) • h]. The area under the AF concentration-time curve (AUC_0-∞ ascites) in group B was 141 ± 37 (}i, g/ml) • h. The penetration ratio into AF expressed as AUCq^, ascites/AUC^ serum was 0.78 ± 0.1.

Peritoneal pharmacokinetics of cefepime in laparotomy patients with inflammatory bowel disease, and dosage considerations for surgical intra-abdominal infections based on pharmacodynamic assessment

“…The penetration value was greater with cefepime (0.90 ± 0.10, 16,17 or cefodizime (0.78 ± 0.10, n = 6). 18 In the fi nal population pharmacokinetic model with good predictive performance (Fig. 2), the result that θ Q3 was greater than θ Cl and θ Q2 (Table 4) also indicates a high peritoneal penetration.…”

Pharmacokinetics and Tolerability of Zibotentan in Patients with Concurrent Moderate Renal and Moderate Hepatic Impairment

“…The amount of unchanged drug, percentage of unchanged drug and renal clearance was 18.3, 18.3 and 8.8%, respectively, of that of healthy controls in participants with impairment, indicating impaired renal function mainly contributed to differences in clearance and exposure. In addition, the majority of participants with impairment had ascites, which may have contributed to a longer t max and t ½ λz [ 32 , 33 ]. These findings demonstrate how concurrent renal and hepatic impairment can impact PK and highlight the importance of investigating the effects of drugs in this patient population.…”

“…org/ 10. 1186/ 1472-6904-11-3, licensed under CC BY 2.0 () and published under licence to BioMed Central Ltd. Glomerular filtration rate categories (mL/min/1.73 m 2 ) were as follows: G1-normal or high (≥ 90), G2-mildly decreased (60-89), G3a-mildly to moderately decreased (45-59) and G3bmoderately to severely decreased (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). Predictions for the mean CL/F versus baseline eGFR, and associated 95% CIs, used model averaging on a dataset containing data from participants in the renal impairment and the hepatic impairment study (n = 80) (i.e., data available prior to conducting the combined renal and hepatic impairment study) as well as to a dataset containing data from participants in the renal, the hepatic and the combined impairment study (n = 103) (i.e., data available after conducting the combined renal and hepatic impairment study).…”

Pharmacokinetics of cefodizime following single doses of 0.5, 1.0, 2.0, and 3.0 grams administered intravenously to healthy volunteers

“…These results are in agreement with, and extend, those obtained by Dagrosa and coworkers, who investigated the pharmacokinetics of cefodizime in healthy male volunteers after single-dose intravenous administration (dose range, 0.5 to 2.0 g) (4). The linear pharmacokinetics of cefodizime facilitate the prediction of the effects of dosage adjustments, for example, in patients with renal or hepatic impairment (6,7).…”