Penetration of doripenem in human brain: an observational microdialysis study in patients with acute brain injury.
Concentration-time profiles of unbound doripenem were determined by microdialysis in the cerebral interstitium of five patients with acute brain injury. The ratio of the area under the concentration-time curve in brain to that in plasma (AUC(brain)/AUC(plasma)) was 0.17 in one patient and 0.01 in the remaining four patients. Based on the percentage of the dosing interval during which the doripenem concentration exceeded a certain minimum inhibitory concentration (T>MIC), a value of ≥35% of the dosing interval was reached for pathogens with MICs up to 0.05 mg/L. The present data indicate that breakpoints based on concentrations of doripenem in plasma may overestimate antimicrobial activity in brain parenchyma.
Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University Vienna, Vienna, Austria.
Wolfgang
W
Poeppl
Markus
M
Zeitlinger
Oliver
O
Donath
Gabriele
G
Wurm
Markus
M
Müller
Florin
F
Botha
Udo M
UM
Illievich
Heinz
H
Burgmann
D000368:Aged; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000493:pharmacokinetics; D019540:Area Under Curve; D001419:Bacteria / Q000472:pathogenicity; D001424:Bacterial Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D001921:Brain / Q000378:metabolism* / Q000382:microbiology; D001930:Brain Injuries / Q000378:metabolism*; D015780:Carbapenems / Q000378:metabolism / Q000493:pharmacokinetics*; D000077726:Doripenem; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D017551:Microdialysis; D008875:Middle Aged; D010949:Plasma / Q000378:metabolism; D013997:Time Factors
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem