[Pharmacokinetics of fusidic acid in patients with seriously infected burns].
The pharmacokinetics of fusidic acid (FA) were studied in 10 infected severe burns patients (35 +/- 5 yrs, 81 +/- 17 kg) i.e. 43 +/- 10% in 3rd degree. Treatment was given at the dose of 500 mg/8 hours (2-hour infusion). The kinetics of FA were evaluated on D1 (1st infusion) and at steady state on D4 (10th infusion), each sequence involving 9 whole blood samples. Samples were assayed by high-performance liquid chromatography. Data were analysed by a non-compartmental method. Mean duration of treatment, considered effective in all cases, was 5.9 +/- 2.1 days. The systemic safety of FA was felt to be good. Kinetic analysis revealed the existence of significant differences between D1 and D4 concerning the parameters Cmax, Cmin, AUC, Cl and Vss. These events are attributable to the non-linear nature of the human kinetics of FA. Accumulation ratios R1 and R2 did not differ i.e. 1.51 +/- 0.25 and R2 = 2.44 +/- 0.68. Kinetic modelling based upon the experimental tracing obtained on D1 revealed good coincidence of the predictive tracing in relation to data determined on D4. The dosage algorithm of 500 mg/8 hours was microbiologically satisfactory with Cmin measured on D1 and at steady state constantly greater than the MIC of the main organisms concerned (< to 2 micrograms/ml). Reduction in the parameters Cmax and AUC in comparison with a group of healthy subjects ultimately led to shortening of the mean T1/2 of FA. In the absence of impaired liver function, this is attributable to the known increase in hepatic clearances in burns patients and, to a certain extent, to the existence of translesional extra-hepatic clearance, which could contribute to the success of treatment.
Service de Pharmacie Clinique, G.H. Necker-Enfants Malades, Paris, France.
A
A
Lesne-Hulin
P
P
Bourget
H
H
Le Bever
H
H
Carsin
D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000209:etiology; D002056:Burns / Q000150:complications*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000209:etiology; D005672:Fusidic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D008657:Metabolic Clearance Rate; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000209:etiology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000209:etiology
D000900:Anti-Bacterial Agents; D005672:Fusidic Acid
Pharmacocinétique de l'acide fusidique administré au sujet gravement brûlé infecté.