Population kinetic–pharmacodynamic analysis of serum potassium in patients receiving sulfamethoxazole/trimethoprim

Autor: Toshinori Hirai, Chihiro Shiraishi, Sumire Nakai, Miu Ushiro, Kazuhiko Hanada, Takuya Iwamoto
Rok vydání: 2022
Předmět:
Zdroj: Basic & Clinical Pharmacology & Toxicology. 131:380-391
ISSN: 1742-7843
1742-7835
DOI: 10.1111/bcpt.13783
Popis: Since trimethoprim (TMP) dose-dependently inhibits the excretion of potassium, a population kinetic-pharmacodynamic analysis was performed to establish an adequate dosing schedule and characterize factors of hyperkalaemia. Dataset was constructed using a retrospective observational cohort of hospitalized patients (18 years) with oral sulfamethoxazole/trimethoprim formulation. The model integrated a kinetic model for TMP, a urinary TMP concentration-response curve and a kinetic model for serum potassium using an indirect response model. The model was a function of body weight, renal function, serum potassium levels and TMP dosing schedule. We evaluated covariates by the stepwise forward and backward selection methods. The Monte Carlo simulation determined the probability of hyperkalaemia (5.5 or6.0 meq/L) according to the dosing schedule, renal function and covariates. This study included 317 patients [age 62 (42-72) years] with 4359 serum potassium levels. The significant covariate was non-steroidal anti-inflammatory drugs (NSAIDs), with a 72.3% reduction in 50% inhibitory concentration. Monte Carlo simulation revealed that high-dose TMP (400 mg thrice daily) co-administered with NSAIDs led to mild hyperkalaemia (10%) and severe hyperkalaemia (approximately 5%), regardless of renal function. In conclusion, clinicians should pay attention to hyperkalaemia with TMP high-dose and co-administered NSAIDs.
Databáze: OpenAIRE
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