The pharmacokinetic of amikacin in critically ill adult and paediatric patients: comparison of once- versus twice-daily dosing regimens.
The pharmacokinetic profile of amikacin was analysed by a two-compartment model in 100 critically-ill adult and paediatric patients with normal renal function. In addition the serum amikacin levels in 200 patients randomized to receive a once- or twice-daily dosing regimen are reported. The mean volume of distribution (Vdt) was 0.33 l/kg in the adult patients, 0.50 l/kg in patients 6 to 12 months of age and 0.58 l/kg in patients less than 6 months old. The elimination half-life was prolonged, being 3.45, 2.86 and 5.02 h for the respective age groups (normal 2 h). The clearances dose/AUC) were 0.051, 0.068 and 0.063 l/h/kg respectively. Within each group of patients there was a large variation in the pharmacokinetic parameters, with the Vdt varying by a factor of 6 and the elimination half-life by a factor of 10. All patients receiving a once-daily dose of amikacin had therapeutic peak concentrations. In comparison, therapeutic concentrations were achieved in only 48% of adult and 44% of the paediatric patients receiving the twice-daily dosing regimen. Furthermore the amikacin trough concentrations were significantly higher in the patients who received a divided daily dose. As a consequence of the pharmacokinetic profile of amikacin in critically ill patients a once-daily dosing regimen may be more effective and less toxic than the conventional twice-daily dosing regimen.
Marik
P E
PE
Intensive Care Unit, Baragwanth Hospital, Johannesburg, South Africa.
Havlik
I
I
Monteagudo
F S
FS
Lipman
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000583:Amikacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; D002439:Cefotaxime / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002442:Ceftazidime / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006088:Gram-Negative Aerobic Bacteria / Q000187:drug effects*; D006801:Humans; D007223:Infant; D007668:Kidney / Q000378:metabolism; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged
D000583:Amikacin; D002442:Ceftazidime; D003404:Creatinine; D002439:Cefotaxime