Population Pharmacokinetics and Dosing Simulations of Ampicillin and Sulbactam in Hospitalised Adult Patients

Setiawan, Eko and Cotta, Menino Osbert and Abdul‑Aziz, Mohd‑Hafiz and Widjanarko, Doddy and Sosilya, Hernycane and Lukas, Dwi Lily and Wallis, Steven C. and Parker, Suzanne and Roberts, Jason A. (2023) Population Pharmacokinetics and Dosing Simulations of Ampicillin and Sulbactam in Hospitalised Adult Patients. Clinical Pharmacokinetics. ISSN 0312-5963; Electronic ISSN 1179-1926

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Abstract

Background The pharmacokinetic variability of ampicillin-sulbactam in adults has not been extensively described, particularly in patients with a reduced renal function (i.e., < 60 mL/min). Objective This study investigated the population pharmacokinetics of ampicillin and sulbactam in patients with a wide range of renal functions and sought to defne dosing approaches that have a high likelihood for optimising drug exposure. Methods Serial blood samples were collected from 16 adult patients receiving intravenous ampicillin-sulbactam in general wards. Total ampicillin and sulbactam concentrations were measured by chromatographic assay and pharmacokinetic parameters were estimated using Pmetrics®. Monte Carlo simulations were used to evaluate the probability of target attainment(PTA) of free ampicillin and sulbactam concentrations exceeding the minimum inhibitory concentration (MIC) for 60% and 100% of the dosing interval. Fractional target attainment (FTA) was calculated against MIC distributions of common hospital pathogens. A threshold of ≥ 90% and ≥ 95% was used to defne both optimal PTA and FTA, respectively. Results The median (range) age, weight, and serum creatinine of the study population was 68 (40–82) years, 62 (40–82) kg, and 1.4 (0.6–6.4) mg/dL, respectively. The pharmacokinetics of ampicillin and sulbactam were best described by a twocompartment model with serum creatinine most closely associated with clearance for both drugs. The estimated ampicillin and sulbactam clearances were 5.58 L/h and 4.79 L/h, respectively, while the volumes of distribution were 12.6 L and 15.36 L, respectively. Approved dosing regimens of ampicillin-sulbactam were sufcient against MICs ≤ 8 and ≤ 4 mg/L, respectively. A 4-h infusion enabled optimal PTA at higher MICs. For both dosing targets, optimal FTAs were obtained against Streptococcus pneumoniae. Conclusion Optimal FTAs were obtained against the susceptible MIC distributions of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Applying a 4-h infusion will enhance PTA and FTA, particularly at higher MICs.

Item Type:	Article
Subjects:	R Medicine > R Medicine (General) R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Pharmacy > Department of Pharmacy
Depositing User:	Eko Setiawan 206023
Date Deposited:	14 Mar 2023 02:34
Last Modified:	20 Mar 2023 04:11
URI:	http://repository.ubaya.ac.id/id/eprint/43569

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