TY - JOUR
T1 - Population pharmacokinetic-pharmacodynamic target attainment analysis of sulbactam in patients with impaired renal function
T2 - Dosing considerations for Acinetobacter baumannii infections
AU - Yokoyama, Yuta
AU - Matsumoto, Kazuaki
AU - Ikawa, Kazuro
AU - Watanabe, Erika
AU - Morikawa, Norifumi
AU - Takeda, Yasuo
N1 - Publisher Copyright:
© 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - This study aimed to perform a pharmacokinetic (PK)-pharmacodynamic (PD) target attainment analysis of sulbactam against Acinetobacter baumannii in patients with impaired renal function. The PK data (188 plasma samples and 27 urine samples) were modeled simultaneously. The mean population parameters were CLr (l/h)=0.0792×CLcr (ml/min), CLnr (l/h)=2.35, Vc (l)=12.2, Q (l/h)=4.68 and Vp (l)=4.44, where CLr and CLnr are the renal and non-renal clearances, Vc and Vp are the distribution volumes of the central and peripheral compartments and Q is intercompartmental clearance. The creatinine clearance (CLcr) was the most significant covariate. The determined MIC of sulbactam against A.baumannii clinical isolates (n=27) was 0.75-6.0μg/ml with MIC50 and MIC90 of 1 and 4μg/ml, respectively. For sulbactam regimens, a Monte Carlo simulation estimated the probabilities of attaining the bactericidal target (60% of the time above the MIC) and determined the PK-PD breakpoints (the highest MICs at which the probabilities were 90% or more). In a patient with a CLcr of 15ml/min, a regimen of 1g twice daily achieved a 90% or more probability against the A.baumannii isolate population; however, 2g four times daily was needed for a 90% or more probability in a patient with a CLcr of 90ml/min. The results of the PK-PD target attainment analysis are useful when choosing the sulbactam regimen based on the CLcr of the patient and the susceptibility of A.baumannii. Registration number: UMIN000007356.
AB - This study aimed to perform a pharmacokinetic (PK)-pharmacodynamic (PD) target attainment analysis of sulbactam against Acinetobacter baumannii in patients with impaired renal function. The PK data (188 plasma samples and 27 urine samples) were modeled simultaneously. The mean population parameters were CLr (l/h)=0.0792×CLcr (ml/min), CLnr (l/h)=2.35, Vc (l)=12.2, Q (l/h)=4.68 and Vp (l)=4.44, where CLr and CLnr are the renal and non-renal clearances, Vc and Vp are the distribution volumes of the central and peripheral compartments and Q is intercompartmental clearance. The creatinine clearance (CLcr) was the most significant covariate. The determined MIC of sulbactam against A.baumannii clinical isolates (n=27) was 0.75-6.0μg/ml with MIC50 and MIC90 of 1 and 4μg/ml, respectively. For sulbactam regimens, a Monte Carlo simulation estimated the probabilities of attaining the bactericidal target (60% of the time above the MIC) and determined the PK-PD breakpoints (the highest MICs at which the probabilities were 90% or more). In a patient with a CLcr of 15ml/min, a regimen of 1g twice daily achieved a 90% or more probability against the A.baumannii isolate population; however, 2g four times daily was needed for a 90% or more probability in a patient with a CLcr of 90ml/min. The results of the PK-PD target attainment analysis are useful when choosing the sulbactam regimen based on the CLcr of the patient and the susceptibility of A.baumannii. Registration number: UMIN000007356.
KW - Acinetobacter baumannii
KW - Dosing regimen
KW - Monte carlo simulation
KW - Population pharmacokinetics
KW - Sulbactam
UR - http://www.scopus.com/inward/record.url?scp=84930378566&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930378566&partnerID=8YFLogxK
U2 - 10.1016/j.jiac.2014.12.005
DO - 10.1016/j.jiac.2014.12.005
M3 - Article
C2 - 25638291
AN - SCOPUS:84930378566
SN - 1341-321X
VL - 21
SP - 284
EP - 289
JO - Journal of Infection and Chemotherapy
JF - Journal of Infection and Chemotherapy
IS - 4
ER -
