Table 1.
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.