Gut microbiota and cardiac arrhythmia: a pharmacokinetic scope

The Egyptian Heart Journal

Table 1 Pharmacokinetic properties of some anti-arrhythmic and antithrombotic drugs commonly used in management of cardiac arrhythmia

			Major route of elimination	Involved cytochrome P450 enzymes	Protein binding %	Transporters	References
Anti-arrhythmic Drugs	Class Ia	Quinidine	Hepatic and renal	CYP3A4, CYP2D6	80	P-glycoprotein, OCT2, OCT3	[47, 52, 53]
		Disopyramide	Renal	CYP3A4	50–65	OCT2, OCT3	[53]
		Procainamide	Hepatic and renal	CYP2D6	20	MATE; OCT3	[53,54,55]
	Class Ib	Lidocaine	Hepatic	CYP1A2, CYP3A4	60–80	OCT3	[53, 55, 56]
		Phenytoin	Hepatic	CYP2C19; CYP2C9	90	OCT3	[53, 57]
		Mexiletine	Hepatic	CYP2D6	70	OCT2, OCT3	[53, 58, 59]
		Tocainide	Hepatic and renal	CYP3A4	50		[60]
	Class Ic	Flecainide	Hepatic and renal	CYP2D6	20	OCT2	[59, 61]
	Class Ic	Propafenone	Hepatic	CYO2D6, CYP3A4	90	OCT2	[59, 62]
	Class II	Esmolol	Blood esterase	…….	55		[63]
	Class II	Metoprolol	Hepatic	CYP2D6			[64]
	Class III	Amiodarone	Hepatic	CYP1A2, CYP2C9, CYP2D6	96	P-glycoprotein, OAT2B1	[47, 65]
		Sotalol	Renal	CYP3A4	0	OCT2	[47, 65, 66]
		Ibutilide	Hepatic and renal	undetermined	…		[67]
		Dofetilide	Hepatic and renal	CYP3A4	60–70	MATE: OCT2	[55, 68]
	Class IV	Verapamil	Hepatic	CYP3AF, CYP3A5	90	P-glycoprotein, OCT2	[47, 52]
	Class IV	Diltiazem	Hepatic	CYP3AF, CYP3A5	70–80	P-glycoprotein	[47, 52]
	Others	Adenosine	Cellular metabolism	……	……		[69]
	Others	Digoxin	Renal	……	20–30	P-glycoprotein	[47, 70]
Antithrombotic		Warfarin	Hepatic	CYP1A2, CYP2C19, CYP3A4	99		[71]
		Aspirin*	Hepatic	CYP2D9	58.3–81.7#	OAT1	[72,73,74]
		Dabigatran	Renal	CYP3A4	35	P-glycoprotein	[70, 75]
		Edoxaban	Renal	….	40–59	P-glycoprotein	[70, 76]
		Rivaroxaban	Hepatic and renal	CYP3A4, CYP3A5, CYP2J2	92–95	P-glycoprotein	[70, 77]
		Apixaban	Hepatic and renal	CYP3A4, CYP1A2, 2C8, 2C9, 2C19	93	P-glycoprotein	[47, 70, 78]

*Other Aspirin metabolizing enzymes: N-acetyl transferase2(NAT2) an UDP-glucuronosyltransferase 1A6(UGT1A6). # The plasma protein binding of aspirin ranges from approximately 58.3 for aspirin and 81.7 for salicylates. MATE multi-drug and toxin extrusion proteins, OAT organic anion transporter, OCT organic cation transporter