Table 1.
Direct metabolism of drugs by gut microbes associated with pharmacokinetic changes
| Drug | Animal/human | In vivo/in vitro | Organism | Effect on PK (intact gut microbiome) | Comments |
|---|---|---|---|---|---|
| Amlodipine [22] | Both | In vivo | N/A | ↓ F, ↓ Tmax, ↓ Cmax, ↓ AUC | Antibiotics may increase bioavailability by suppressing gut microbial metabolic activities |
| Aspirin [23, 24] | Animal |
Both In vivo |
Lysinibacillus sphaericus |
↓ Cmax and AUC ↓ F |
Reduced gut microbial ASA-metabolizing activity by 67% in rats ↑ F in microbiota-depleted mice |
| Diclofenac acyl glucuronide [25] | Animal | Both | Escherichia coli | ↓ Cmax | E. coli β-glucuronidase catalyzed the deconjugation of diclofenac acyl glucuronides in vitro |
| Digoxin [19] | Both | Both | Eggerthella lenta | ↑ F | E. lenta reduces Cgr 2 → less reduction of digoxin |
| Indomethacin [26] | Human | In vitro | Enterobacteriaceae | ↓ Concentrations | β-glucuronidase expression by human gut Enterobacteriaceae |
| Irinotecan [27] | Both | In vitro | Bacteroides uniformis and E. coli | ↑ Abundance (SN-38) | Gut microbial enzymes promote drug toxicity by hydrolyzing the inactive drug → active drug |
| Levodopa [28–30] | Both | In vivo | Enterococcus faecalis and E. lenta | ↓ Levodopa concentration | Microbes cause less levodopa to be available to cross the blood–brain barrier |
| Lovastatin [31] | Both | In vivo | N/A | May increase Cmax, Tmax, and AUC of M8 | The gut microbiota is involved in the metabolism of lovastatin to its bioactive metabolite (M8) |
| Nabumetone [32] | Animal | Both | E. coli | ↓ AUC, Cmax, and half-life | E. coli converts the NSAID to a reduced pharmacologically inactive metabolite |
| Tacrolimus [20] | Human | In vivo | Faecalibacterium prausnitzii | Positive correlation b/w F. prausnitzii abundance and tacrolimus dose | Study did not explore the potential mechanisms by which F. prausnitzii may have influenced tacrolimus metabolism |
| Tacrolimus [21] | Human | In vitro | F. prausnitzii and Clostridiales order |
Tacrolimus → M1 ↓ F |
F. prausnitzii may metabolize tacrolimus into M1 (five-fold less potent than tacrolimus as an immunosuppressant) |
ASA aspirin, AUC area under the concentration–time curve, b/w between, Cgr2 cardiac glycoside reductase operon, Cmax maximum concentration, F relative bioavailability, M1 tacrolimus metabolite, M8 lovastatin metabolite, N/A not available, NSAID non-steroidal anti-inflammatory drug, PK pharmacokinetics, SN-38 active metabolite of irinotecan, Tmax time to maximum concentration, ↓ decreased