Variability of pharmacokinetic parameters in patients receiving different dosages of daptomycin: is therapeutic drug monitoring necessary?
Pharmacokinetic studies of daptomycin in septic patients indicate that pharmacokinetic parameters may be altered. The purpose of this clinical investigation is to determine the pharmacokinetics of daptomycin in a population of hospitalized patients with clinically significant gram-positive infections and receiving daptomycin. Daptomycin was measured using an isocratic HPLC technique. Thirty-five patients suffering from gram-positive severe infections and receiving daptomycin were included in the study. Patients were divided into two groups, depending on the dose of daptomycin received: group A, including 24 patients receiving 6 mg/kg/day daptomycin and group B, 11 patients receiving 8 mg/kg/day. Patients receiving a daptomycin dosage of 8 mg/kg/day had significantly higher values of mean C max and AUC0-24. Each group was further divided into three subgroups, according to the creatinine clearance (CrCl) values: (1) patients with a CrCl >80 ml/min, (2) patients with CrCl ranging between 80 and 40 ml/min, and (3) patients with CrCl <40 ml/min. Compared to patients with normal renal function, those with CrCl <40 ml/min had higher mean values of minimum concentration (C min) (p < 0.001), AUC0-24 (p = 0.03), and prolonged plasma half-time (p < 0.001). These differences were present both in patients receiving 6 and those with 8 mg/kg/day. However, in each of the three subgroups with different degrees of renal function a marked variability of pharmacokinetics parameters was observed. The factors associated with increased mortality were an infection acquired in the ICU, hypoalbuminemia, and AUC/MIC <666. The marked variability that characterizes daptomycin pharmacokinetics in these patients suggest the monitoring of the main pharmacokinetic parameters in this clinical setting.
Departmert of Public Health and Infectious Diseases, Sapienza University of Rome, Policlinico Umberto I, Viale dell'Università 37, 00161, Rome, Italy. marcofalc@libero.it
Marco
M
Falcone
Alessandro
A
Russo
Maria Iris
MI
Cassetta
Angela
A
Lappa
Luigi
L
Tritapepe
Gabriella
G
d'Ettorre
Stefania
S
Fallani
Andrea
A
Novelli
Mario
M
Venditti
D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017576:Daptomycin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods; D024881:Drug Resistance, Bacterial; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D017576:Daptomycin