Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Simulation of Piperacillin/Tazobactam for Dosing Optimization in Late Elderly Patients with Pneumonia
| Autor: | Takahisa Yano, Fumi Karino, Takeshi Isobe, Kiyotaka Miura, Hiroki Tamaki, Norifumi Morikawa, Kazuro Ikawa, Nobuhiro Nishimura, Noriyuki Ishihara, Kohji Naora |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) medicine.medical_specialty population pharmacokinetic/pharmacodynamic analysis 030106 microbiology Population Urology Renal function 030226 pharmacology & pharmacy Biochemistry Microbiology Tazobactam Article 03 medical and health sciences 0302 clinical medicine Pharmacokinetics tazobactam medicine piperacillin pneumonia Pharmacology (medical) General Pharmacology Toxicology and Pharmaceutics education late elderly patients population pharmacokinetic pharmacodynamic analysis education.field_of_study business.industry lcsh:RM1-950 NONMEM Infectious Diseases lcsh:Therapeutics. Pharmacology Pharmacodynamics Piperacillin/tazobactam business Piperacillin medicine.drug |
| Zdroj: | Antibiotics, Vol 9, Iss 3, p 113 (2020) Antibiotics Volume 9 Issue 3 |
| ISSN: | 2079-6382 |
| Popis: | The aim of this study was to develop a population pharmacokinetic model for piperacillin (PIPC)/tazobactam (TAZ) in late elderly patients with pneumonia and to optimize the administration planning by applying pharmacokinetic/pharmacodynamic (PK/PD) criteria. PIPC/TAZ (total dose of 2.25 or 4.5 g) was infused intravenously three times daily to Japanese patients over 75 years old. The plasma concentrations of PIPC and TAZ were determined using high-performance liquid chromatography and modeled using the NONMEM program. PK/PD analysis with a random simulation was conducted using the final population PK model to estimate the probability of target attainment (PTA) profiles for various PIPC/TAZ-regimen&ndash minimum-inhibitory-concentration (MIC) combinations. The PTAs for PIPC and TAZ were determined as the fraction that achieved at least 50% free time > MIC and area under the free-plasma-concentration&ndash time curve over 24 h &ge 96 &mu g h/mL, respectively. A total of 18 cases, the mean age of which was 86.5 ± 6.0 (75&ndash 101) years, were investigated. The plasma-concentration&ndash time profiles of PIPC and TAZ were characterized by a two-compartment model. The parameter estimates for the final model, namely the total clearance, central distribution volume, peripheral distribution volume, and intercompartmental clearance, were 4.58 + 0.061 × (CLcr &minus 37.4) L/h, 5.39 L, 6.96 L, and 20.7 L/h for PIPC, and 5.00 + 0.059 × 37.4) L/h, 6.29 L, 7.73 L, and 24.0 L/h for TAZ, respectively, where CLcr is the creatinine clearance. PK/PD analysis using the final model showed that in drug-resistant strains with a MIC > 8 &mu g/mL, 4.5 g of PIPC/TAZ every 6 h was required, even for the patients with a CLcr of 50&ndash 60 mL/min. The population PK model developed in this study, together with MIC value, can be useful for optimizing the PIPC/TAZ dosage in the over-75-year-old patients, when they are administered PIPC/TAZ. Therefore, the findings of present study may contribute to improving the efficacy and safety of the administration of PIPC/TAZ therapy in late elderly patients with pneumonia. |
| Databáze: | OpenAIRE |
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