Pharmacokinetic evaluation of oxaliplatin combined with S-1 (SOX) chemotherapy in a rat model of colorectal cancer with acute kidney injury: Predictive renal biomarkers for dose optimization

This study investigated the pharmacokinetics of SOX chemotherapy and renal biomarkers in rats.AKI was prepared by renal ischemia-reperfusion injury in 1,2-dimethylhydrazine-induced colorectal cancer model rats. Serum creatinine (sCr) levels were determined as a renal biomarker. After administration of S-1 (2 mg/kg tegafur) and oxaliplatin (5 mg/kg), drug concentrations of tegafur, 5-FU, and platinum were measured in the plasma and tumors.No alterations in the area under the plasma concentration-time curve (AUC0-24h ) values of 5-fluorouracil were observed between control and AKI model rats. The tumor concentrations of 5-fluorouracil in the mild and severe AKI groups were significantly lower than control group. The AUC0-24h for platinum increased with AKI severity. Notably, population pharmacokinetic analysis identified sCr as a covariate in platinum distribution after SOX chemotherapy.To optimize dose adjustment of SOX chemotherapy in patients with AKI, sCr may be a key factor in determining the appropriate dose.PMID:37966716 | DOI:10.1080/00498254.2023.2283736
Source: Xenobiotica - Category: Research Authors: Source Type: research