Commensal Gut Bacteria Convert the Immunosuppressant Tacrolimus to Less Potent Metabolites

• Published in: Drug metabolism and disposition Vol. 47; no. 3; pp. 194 - 202
• Main Authors: Guo, Yukuang, Crnkovic, Camila Manoel, Won, Kyoung-Jae, Yang, Xiaotong, Lee, John Richard, Orjala, Jimmy, Lee, Hyunwoo, Jeong, Hyunyoung
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2019; American Society for Pharmacology and Experimental Therapeutics, Inc; The American Society for Pharmacology and Experimental Therapeutics
• Subjects: Administration, Oral; Adult; Adults; Aged; Bacteria; Cells, Cultured; Dosage; Dose-Response Relationship, Drug; Faecalibacterium prausnitzii - metabolism; Feces - chemistry; Female; Gastrointestinal Microbiome - physiology; Graft Rejection - immunology; Graft Rejection - prevention & control; Healthy Volunteers; Humans; Immunosuppression Therapy - methods; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - analysis; Immunosuppressive Agents - metabolism; Kidney transplantation; Kidney Transplantation - adverse effects; Kidneys; Leukocytes (mononuclear); Leukocytes, Mononuclear - drug effects; Magnetic resonance spectroscopy; Male; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; Microsomes; Middle Aged; NMR; Nuclear magnetic resonance; Peripheral blood mononuclear cells; Pharmacology; Purification; Symbiosis; Tacrolimus; Tacrolimus - administration & dosage; Tacrolimus - analysis; Tacrolimus - metabolism; PBS; P-gp; rRNA; m/z; OD600; MS/MS; PBMC; HPLC

Tacrolimus exhibits low and variable drug exposure after oral dosing, but the contributing factors remain unclear. Based on our recent report showing a positive correlation between fecal abundance of Faecalibacterium prausnitzii and oral tacrolimus dose in kidney transplant patients, we tested wheth...