TY - JOUR
T1 - Dosing optimization of ampicillin-sulbactam based on cystatin C in elderly patients with pneumonia
AU - Matsubara, Kayoko
AU - Matsumoto, Kazuaki
AU - Yokoyama, Yuta
AU - Watanabe, Erika
AU - Enoki, Yuki
AU - Shigemi, Akari
AU - Ikawa, Kazuro
AU - Terazono, Hideyuki
AU - Morikawa, Norifumi
AU - Ohshige, Tamao
AU - Takeda, Yasuo
N1 - Publisher Copyright:
© 2021 The Pharmaceutical Society of Japan.
PY - 2021/5
Y1 - 2021/5
N2 - Ampicillin-sulbactam is a first-line therapy for pneumonia and is mainly excreted by the kidney. It is important to optimize the dose and dosing interval of ampicillin-sulbactam because in patients with decreased renal function and low skeletal muscle mass, such as the elderly, excess drug may burden renal function. In this study, we evaluated indices of renal function and optimized the dose and dosing interval of ampicillin-sulbactam based on pharmacokinetics (PK) and pharmacodynamics theory in elderly patients. The serum concentrations of ampicillin and sulbactam were measured by HPLC, and PK parameters were calculated. Correlations between the clearance of ampicillin or sulbactam and renal function were evaluated, and dosing optimization was calculated based on PK parameters. The PK parameters of ampicillin were CL=6.5±4.0L/h, Vd=19.3±0.2L, Ke=0.4±0.2, and t1/2=2.7±1.6h. The most correlated renal function index was estimated glomerular filtration rate (eGFRcys-c) calculated by serum cystatin-c (r=0.7374, correlation formula; CL of ampicillin=0.1937×eGFRcys-c-0.6726). Based on this formula, we calculated the clearance of ampicillin and developed dosing regimens for the elderly. Serum cystatin-c concentration is an ideal index to optimize ampicillin-sulbactam antimicrobial therapy in elderly patients with pneumonia.
AB - Ampicillin-sulbactam is a first-line therapy for pneumonia and is mainly excreted by the kidney. It is important to optimize the dose and dosing interval of ampicillin-sulbactam because in patients with decreased renal function and low skeletal muscle mass, such as the elderly, excess drug may burden renal function. In this study, we evaluated indices of renal function and optimized the dose and dosing interval of ampicillin-sulbactam based on pharmacokinetics (PK) and pharmacodynamics theory in elderly patients. The serum concentrations of ampicillin and sulbactam were measured by HPLC, and PK parameters were calculated. Correlations between the clearance of ampicillin or sulbactam and renal function were evaluated, and dosing optimization was calculated based on PK parameters. The PK parameters of ampicillin were CL=6.5±4.0L/h, Vd=19.3±0.2L, Ke=0.4±0.2, and t1/2=2.7±1.6h. The most correlated renal function index was estimated glomerular filtration rate (eGFRcys-c) calculated by serum cystatin-c (r=0.7374, correlation formula; CL of ampicillin=0.1937×eGFRcys-c-0.6726). Based on this formula, we calculated the clearance of ampicillin and developed dosing regimens for the elderly. Serum cystatin-c concentration is an ideal index to optimize ampicillin-sulbactam antimicrobial therapy in elderly patients with pneumonia.
KW - Ampicillin-sulbactam
KW - Creatinine
KW - Cystatin-c
KW - Pharmacokinetics–pharmacodynamics
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U2 - 10.1248/bpb.b20-00781
DO - 10.1248/bpb.b20-00781
M3 - Article
C2 - 33952829
AN - SCOPUS:85105368615
SN - 0918-6158
VL - 44
SP - 732
EP - 736
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
IS - 5
ER -