Details

Autor(en) / Beteiligte

• Dukaew, Nahathai
• Thongkumkoon, Patcharawadee
• Sirikaew, Nutnicha
• Dissook, Sivamoke
• Sakuludomkan, Wannachai
• Tongjai, Siripong
• Thiennimitr, Parameth
• Na Takuathung, Mingkwan
• Benjanuwattra, Juthipong
• Kongthaweelert, Prachya
• Koonrungsesomboon, Nut

Titel

Gut Microbiota-Mediated Pharmacokinetic Drug-Drug Interactions between Mycophenolic Acid and Trimethoprim-Sulfamethoxazole in Humans

Ist Teil von

• Pharmaceutics, 2023-06, Vol.15 (6), p.1734

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2023

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Mycophenolic acid (MPA) and trimethoprim-sulfamethoxazole (TMP-SMX) are commonly prescribed together in certain groups of patients, including solid organ transplant recipients. However, little is known about the pharmacokinetic drug-drug interactions (DDIs) between these two medications. Therefore, the present study aimed to determine the effects of TMP-SMX on MPA pharmacokinetics in humans and to find out the relationship between MPA pharmacokinetics and gut microbiota alteration. This study enrolled 16 healthy volunteers to take a single oral dose of 1000 mg mycophenolate mofetil (MMF), a prodrug of MPA, administered without and with concurrent use of TMP-SMX (320/1600 mg/day) for five days. The pharmacokinetic parameters of MPA and its glucuronide (MPAG) were measured using high-performance liquid chromatography. The composition of gut microbiota in stool samples was profiled using a 16S rRNA metagenomic sequencing technique during pre- and post-TMP-SMX treatment. Relative abundance, bacterial co-occurrence networks, and correlations between bacterial abundance and pharmacokinetic parameters were investigated. The results showed a significant decrease in systemic MPA exposure when TMP-SMX was coadministered with MMF. Analysis of the gut microbiome revealed altered relative abundance of two enriched genera, namely the genus and , following TMP-SMX treatment. The relative abundance of the genera , group, group, and appeared to be significantly correlated with systemic MPA exposure. Coadministration of TMP-SMX with MMF resulted in a reduction in systemic MPA exposure. The pharmacokinetic DDIs between these two drugs were attributed to the effect of TMP-SMX, a broad-spectrum antibiotic, on gut microbiota-mediated MPA metabolism.