Pharmacokinetics of teicoplanin in an ICU population of children and infants.
OBJECTIVE
Better dosing is needed for antibiotics, including teicoplanin (TEI), to prevent emergence of resistant bacterial strains. Here, we assess the TEI pharmacokinetics (PK) related to a 10 mg/l minimum inhibitory concentration (MIC) target in ICU children (4 to 120 months; n = 20) with gram+ infections.


METHODS
Standard administration of TEI was with three 10 mg/kg Q12h, loading infusions, and maintainance with 10 mg/kg or 15 mg/kg Q24h. During maintenance, 9 samples (3/day) were collected per patient and the PK analyzed with Nonlinear Mixed Effects Model (NONMEM).


RESULTS
Thirty-five percent of concentrations in older children (> or =2 months) vs. 8% in younger infants (<12 months) were below the target MIC. The global bicompartmental population PK parameters were [mean (interindividual CV%)] CL = 0.23 l/h [72%], V = 3.16 l [58%], k12 = 0.23 h(-1), and k21 = 0.04 h(-1). Two PK subpopulations were identified. The older children had CL = 0.29 [23%] l/h, V = 3.9 l and the younger infants, CL = 0.09 [37%] l/h, V = 1.05 l. Residual error was reduced from 52% to around 30% in the final models.


CONCLUSIONS
Older children in the ICU may require relatively higher doses of teicoplanin. However, a study in a larger population is needed.
Lukas
John C
JC
Laboratory of Biopharmaceutics and Pharmacokinetics, School of Pharmacy, University of Athens, Zografou 15771, Athens, Greece. jlukas@ath.forthnet.gr
Karikas
Georgios
G
Gazouli
Maria
M
Kalabalikis
Panagiotis
P
Hatzis
Tasos
T
Macheras
Panos
P
D000375:Aging / Q000378:metabolism; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D007223:Infant; D007362:Intensive Care Units; D008297:Male; D015233:Models, Statistical; D009010:Monte Carlo Method; D011153:Population; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D017334:Teicoplanin / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D017334:Teicoplanin