Table 1.
Biotransformation of Drugs/Drug Metabolites Performed by the Gut Microbiota*
| Biotransformation | Drug/Metabolite | Comments | Ref |
|---|---|---|---|
| Reduction | |||
| Balsalazide | Azo bond reduction | 22 | |
| Bromezepam | Nitro-reduction | 26 | |
| Clonazepam | Nitro-reduction | 25 | |
| Chloramphenicol | Nitro-reduction | 30 | |
| Digoxin | Double bond reduction | 47–54 | |
| Eltrombopag | Hydrazone cleavage | 37 | |
| Ipsalazide | Azo bond reduction | 22 | |
| levosimendan | Hydrazone cleavage | 35–36 | |
| Loperamideoxide | N-oxide reduction | 43 | |
| Metronidazole | Nitro reduction | 27–29 | |
| Misonidazole | Nitro-reduction | 33 | |
| Neoprontosil | Azo bond reduction | 18 | |
| Nitrazepam | Nitro-reduction | 24 | |
| Nizatidine | N-oxide reduction | 45 | |
| Olsalazine | Azo bond reduction | 22 | |
| Omeprazole | Sulphoxide reduction | 39 | |
| Potassium 1,2,3,4-tetrahydro-2,4-dioxo-1,3,5-triazine-6-carboxylate (potassium oxonate) | 46 | ||
| Prontosil | Azo bond reduction | 17,18 | |
| Ranitidine | N-oxide reduction | 44 | |
| Risperidone | benzisoxazole ring reduction | 42 | |
| Sulfasalazine | Azo bond reduction | 19,20 | |
| Sulfinpyrazone | Sulphoxide reduction | 38 | |
| Sulindac | Sulphoxide reduction | 38 | |
| Zonisamide | Benzisoxazole ring reduction | 40,41 | |
| Hydrolysis | |||
| azetirelin | Proteolysis | 76,77 | |
| calcitonin | Proteolysis | 74 | |
| Diclofenac glucuronide | Hydrolysis to diclofenac | 91,92 | |
| indomethacin glucuronide | Hydrolysis to indomethacin | 92 | |
| insulin | Proteolysis | 74–75 | |
| Irinotecan metabolite SN-38 glucuronide | Glucuronide hydrolysis | 83–90 | |
| Ketoprofen glucuronide | Hydrolysis to ketoprofen | 92 | |
| methotrexate | Production of 4-amino-4-deoxy-N10 -methylpteroic acid | 72–73 | |
| sodium picosyulphate, | Desulfation to 4,4'-dihydroxy -diphenyl-(2 pyridyl)-methane | 78 | |
| Sorivudine (1-beta-D-arabinofuranosyl-5-(E)-(2-bromovinyl)uracil) | Hydrolysis to (E)-5-(2-bromo -vinyl)uracil | 94 | |
| Deacylation | |||
| bucetin | Formation of phenitidine | 56 | |
| Phenacetin, | Formation of phenitidine | 56 | |
| Acetaminophen (paracetamol) | Formation of p-aminophenol | 56 | |
| Demethylation | |||
| methamphetamine | N-Demethylation | 55 | |
| 4’-hydroxy methamphetamine | N-Demethylation | 55 | |
| O-Dealkylation | |||
| Fostamatinib | O-Demethylation of the metabolite R529 | 57 | |
| Dehydroxylation | |||
| Fostamatinib | Dehydroxylation of the metabolite R529 | 57 | |
| L-Dopa (levodopa, L-3,4-dihydroxy-phenylalanine). | Dehydroxylation | 60,61 | |
| Decarboxylation | |||
| L-Dopa (levodopa, L-3,4-dihydroxy-phenylalanine) | 64,65 | ||
| Deamination | |||
| 5-Fluorocytosine | Deamination to 5-fluorouracil | 58,59 | |
| Oxidation | |||
| Levamisole | Thiazole ring-opening | 69 | |
| Lovastatin | Hydroxylated metabolites | 71 | |
| Acetylation | |||
| 5-Aminosalicylic acid | Production of N-acetyl-5-amino salicylic acid | 100–103 | |
| Sulfapyridine | Production of N-acetyl -sulfapyridine | 101 |
•
This table represents a summary of the examples discussed in this review and is not designed to be, nor is it, comprehensive as e.g., any drug (or its metabolites) secreted into the bile as a sulfate or glucuronide will be liable to deconjugation by the gut microbiota.