Notario Dion, Munzir Angela Marietha, Novella Yulina, Hananta Linawati
Department of Pharmacy, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia.
Department of Pharmacology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia.
ADMET DMPK. 2024 Jun 27;12(3):543-551. doi: 10.5599/admet.2358. eCollection 2024.
Cotrimoxazole, a commonly prescribed antibiotic, has substantial resistance, especially in Indonesia, with its uropathogenic resistance reaching 67% in 2017. Although cotrimoxazole has been suggested to be co-administered with lactoferrin to enhance its antibacterial effectiveness and this practice has been widely adopted since the Covid-19 pandemic, the impact of lactoferrin on the pharmacokinetics of cotrimoxazole remains relatively unknown. This study aims to conduct a preliminary clinical investigation into the impact of lactoferrin supplementation on the pharmacokinetics of cotrimoxazole, focusing on the elimination rate and excretion of unchanged drug in urine.
This study employed a blinded, cross-over, single-dose pharmacokinetics investigation, which included five healthy volunteers as participants. In the initial period, the first group received cotrimoxazole (80 mg trimethoprim and 400 mg sulfamethoxazole) along with a lactoferrin-containing supplement, while the second group only received cotrimoxazole. Subsequently, after a washout period, the conditions were reversed. Urine sampling was conducted at intervals from 0 to 24 hours post-medication, and drug levels in the urine were determined using high-performance liquid chromatography.
The population-based pharmacokinetic analysis revealed that the optimal model was the one-compartment model with first-order elimination and proportional residual error.
The findings show that the administration of lactoferrin-containing supplements did not significantly influence the covariate model and, therefore, did not alter the pharmacokinetics parameter of cotrimoxazole in urine with a single administration, implying that lactoferrin did not cause drug interaction problems when given simultaneously.
复方新诺明是一种常用抗生素，耐药性严重，尤其是在印度尼西亚，2017年其对尿路致病菌的耐药率达67%。尽管有人建议将复方新诺明与乳铁蛋白联合使用以增强其抗菌效果，且自新冠疫情以来这种做法已被广泛采用，但乳铁蛋白对复方新诺明药代动力学的影响仍相对未知。本研究旨在对补充乳铁蛋白对复方新诺明药代动力学的影响进行初步临床研究，重点关注尿液中药物的消除率和原形药物排泄情况。
本研究采用盲法、交叉、单剂量药代动力学研究，纳入5名健康志愿者作为参与者。在初始阶段，第一组接受复方新诺明（80mg甲氧苄啶和400mg磺胺甲恶唑）及含乳铁蛋白的补充剂，而第二组仅接受复方新诺明。随后，经过洗脱期后，两组情况互换。给药后0至24小时每隔一段时间进行尿液采样，并使用高效液相色谱法测定尿液中的药物水平。
基于人群的药代动力学分析表明，最佳模型是具有一级消除和比例残差误差的单室模型。
研究结果表明，服用含乳铁蛋白的补充剂对协变量模型无显著影响，因此单次给药时不会改变复方新诺明在尿液中的药代动力学参数，这意味着同时给予乳铁蛋白不会引起药物相互作用问题。
