Pharmacokinetics and Renal Safety Evaluation of Colistin Methanesulfonate Sodium in Korean Healthy Male Volunteers: An Open-Label, Multiple-Dose Study.

PURPOSE: The objective of this study was to evaluate the pharmacokinetics and renal safety of colistin methanesulfonate sodium (CMS) following single and multiple intravenous administrations in healthy Korean male volunteers. This study provides pharmacokinetic and safety information on an Asian population, where data on polymyxins remain limited.

PATIENTS AND

METHODS

This open-label, single- and multiple-dose pharmacokinetic study enrolled 12 subjects, 11 of whom received CMS, and one withdrew prior to dosing. Five doses of CMS 150 mg potency (equivalent to 150 mg colistin) were administered over 2.5 days as 1-h infusions every 12 h, diluted in 50 mL of normal saline. Serial blood samples were collected at predetermined time points to measure plasma colistin concentrations using a validated liquid chromatography-tandem mass spectrometry method. Renal safety was assessed through serial measurements of serum creatinine, blood urea nitrogen, and renal biomarkers. Serum biomarkers included cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), while urinary biomarkers included clusterin, kidney injury molecule-1, N-acetyl-β-D-glucosaminidase, and NGAL.

RESULTS

CMS reached peak levels rapidly with minimal accumulation (accumulation index 0.91 [95% CI, 0.80-1.03]) and a consistent half-life of 2.3 h after both single and multiple dosing, whereas colistin showed progressive accumulation (accumulation index 1.4 [1.32-1.48]) and a half-life increase from 3.6 to 4.5 h. Renal biomarkers, including creatinine, blood urea nitrogen, cystatin C, and NGAL, showed no clinically relevant changes. Although urinary markers were transiently elevated, they remained within reference ranges throughout the study period. Overall, repeated CMS administration was well tolerated, and no evidence of nephrotoxicity was observed.

CONCLUSION

Intravenous administration of CMS resulted in evaluable pharmacokinetic profiles in healthy Korean male volunteers. Although no biomarker-based evidence of nephrotoxicity was detected, these findings should be interpreted with caution, given the small sample size and short study duration. These results may support evidence for renal safety assessments in future studies.