Table 1. Impact of the intestinal microflora on drug pharmacokinetics.

Drug	Pharmacotherapeutic classification	Effect of the gut microbiota on drug pharmacokinetics	Implicated microbe or microbial enzyme (if known)	Postulated effect of the gut microbiota on drug bioavailability (F)/activity/toxicity	Ref
Amiodarone	Class III antiarrhythmic	↑ absorption	Escherichia coli Nissle 1917	↑ F	[13]
Calcitonin	Calciotropic hormone	↑ metabolism (proteolysis)		↓ F and activity	[42]
Diclofenac	Non-steroidal antiinflammatory drug	↑ metabolism (deglucuronidation) and delayed excretion	β-glucuronidase enzymes	↑ toxicity (enterohepatic circulation)	[16]
Digoxin	Cardiac glycoside	↑ metabolism (reduction)	Eggerthella lenta	↓ F and cardiac response	[18][19][20]
Indomethacin	Non-steroidal anti-inflammatory drug	↑ metabolism (deglucuronidation) and delayed excretion	β-glucuronidase enzymes	↑ toxicity (enterohepatic circulation)	[16]
Insulin	Anti-diabetic drug	↑ metabolism (proteolysis)	Protease enzymes	↓ F and activity	[42]
Irinotecan	Topoisomerase I inhibitor	↑ metabolism (deglucuronidation) and delayed excretion	β-glucuronidase enzymes produced by bacteria, including Escherichia coli, Bacteroides vulgatus and Clostridium ramosum	↑ toxicity (regeneration of active SN-38 within the intestinal lumen)	[14]
Ketoprofen	Non-steroidal antiinflammatory drug	↑ metabolism (deglucuronidation) and delayed excretion	β-glucuronidase enzymes	↑ toxicity (enterohepatic circulation)	[16]
Levodopa	Anti-parkinson	1. ↓ absorption 2. ↑ metabolism (dehydroxylation)	1. Helicobacter pylori	↓ F and activity	1.[36][37][38][39] 2.[35]
Loperamide oxide	Anti-propulsive	↑ metabolism (reduction)		↑ activity (prodrug activation)	[43]
Lovastatin	HMG-CoA-reductase inhibitor	↑ metabolism (hydrolysis)		↑ F of active β-hydroxy acid metabolite, therefore, potentially ↑ pharmacological effect	[12]
Metronidazole	Anti-protozoal and antibacterial	↑ metabolism (reduction)		↑ toxicity	[44]
Nitrazepam	Benzodiazepine	↑ metabolism (nitroreduction)	Nitroreductase enzymes	↑ toxicity (postulated association with nitrazepam-induced teratogenicity in rats)	[45]
Nizatidine	H2-receptor antagonist	↑ metabolism (cleavage of N-oxide bond)		↓ systemic F	[46]
Olsalazine	Aminosalicylate	↑ metabolism (reduction)	Azoreductase enzymes	↑ activity (prodrug activation)	[47]
Paracetamol	Analgesic and antipyretic	↓ metabolism (p-Cresol-mediated competitive sulfonation)	Clostridium difficile and others	↑ risk of hepatotoxicity	[21]
Prontosil	Sulfa drug	↑ metabolism (reduction)	Azoreductase enzymes	↑ activity (prodrug activation)	[8]
Ranitidine	H2-receptor antagonist	↑ metabolism (cleavage of N-oxide bond)		↓ systemic F	[46]
Risperidone	Antipsychotic	↑ metabolism (scission of the isoxazole ring)			[48]
Sulfasalazine	Aminosalicylate	↑ metabolism (reduction)	Azoreductase enzymes	↑ activity due to liberation of active 5-aminosalicyclic acid. Also, potentially ↑ toxicity due to enhanced generation of sulfapyridine, which can be systemically absorbed	[10]
Zonisamide	Antiepileptic	↑ metabolism (reduction)	Clostridium sporogenes, Bifidobacterium bifidum, Bacteroides vulgatus, Escherichia coli, Salmonella typhimurium, Pseudomonas fluorescens, Lactobacillus rhamnosus, Streptococcus faecalis		[49]