Table 4.

Pharmacokinetic studies of antiarrhythmics in patients with heart failure and controls

Drug, dose, route of administration, reference	Study group, size, NYHA class, age and sex	Renal disease *	Hepatic disease *	F	C max	C ss	T max	V D	CL	t 1/2	AUC
Cibenzoline, 80 mg, oral and i.v. a 58	HF: n = 6, NYHA II‐III, age 57 ± 8 years, 6M/0FC: n = 5, age 58 ± 11 years, 5M/0F	No	No	→	→	n/a	→	→	→	→	→
Disopyramide, 150 mg i.v. bolus, 18–24 mg h −1 i.v. infusion 59	HF: n = 13, NYHA n/a, age 52–89 years, M/F n/aC: n = 22, age 48–90 years, M/F n/a	No	No	n/a	n/a	→	n/a	→	→	→	n/a
Ibutilide, 1 mg, i.v. 85	HF: n = 6b, NYHA II‐III, 53 ± 17 years, 3M/3FC: n = 10b, age 61 ± 19 years, 8M/2F	No	No	n/a	→	n/a	n/a	→	→	→	→
Lidocaine, 50–100 mg, i.v. 42	HF: n = 8, NYHA n/a, age 44–73 years, M/F n/aC: n = 10, age 24–57 years, 9M/1F	Yes	Yes	n/a	n/a	n/a	n/a	↓ (−33%)	↓ (−37%)	→	n/a
Lidocaine, 100 mg i.v. bolus, 1.4 mg min −1 i.v. infusion 43	HF: n = 7, NYHA n/a, age 61 ± 13 years, 7M/0FC: n = 6, age 50 ± 4 years, 6M/0F	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	↑ (+628%)	n/a
Lidocaine, n/a i.v. bolus, i.v. infusion 14–42 μg kg −1 min −1 60	HF: n = 11, NYHA n/a, age 73 ± 14 years, M/F n/aC: n = 24, age 60 ± 15 years, M/F n/a	No	No	n/a	n/a	n/a	n/a	→	↓ (−36%)	↑ (+62%)	n/a
Mexiletine, n/a, oral 86	PPK: n = 584, age n/a, 412M/172F HF subgroup: n = 210, NYHA I‐IV, age 60 ± 15 years, 157M/53F	n/a	No	n/a	n/a	n/a	n/a	n/a	↓ (−33%)	n/a	n/a
Mexiletine, n/a, oral 61	PPK: n = 58, age 66 ± 12 years, 50M/8FHF subgroup: n = 27, NYHA, age and M/F n/a	n/a	Yes	n/a	n/a	n/a	n/a	→	→	n/a	n/a
Procainamide, 750 mg, i.v. 75	HF: n = 9, NYHA II‐III, age 57 ± 12 years, 6M/3FC: n = 7, age 53 ± 10 years, 4M/3F	No	No	n/a	→	n/a	n/a	→	→	→	→
Procainamide, i.v. infusion 25 mg min −1 62	HF: n = 15, NYHA n/a, age 66 ± 12 years, 14M/1FC: n = 10, age 59 ± 14 years, 9M/1F	No	n/a	n/a	→	n/a	n/a	→	→	→	n/a
Procainamide, n/a, oral and i.v. 63	PPK: n = 39, age 60 ± 14 years, 34M/5FHF subgroup: n = 24, NYHA I, age and M/F n/a	No	No	n/a	n/a	n/a	n/a	→	↓c (−17%)	n/a	n/a
Procainamide, 500 mg, oral 44	HF: n = 20, NYHA n/a, age 55 years, 13M/7FC: n = 20, age 24 ± 1 years, 10M/10F	No	No	n/a	n/a	n/a	n/a	n/a	n/a	↑d (+114%)	n/a
Procainamide, 700–1000 mg i.v. bolus, 3–5 mg min −1 i.v. infusion 64	PPK: n = 20, age 61 ± 9 years, 16M/4FHF subgroup: n = 6, NYHA n/a, age 63 ± 6 years, 4M/2F	Yes	No	n/a	n/a	n/a	n/a	n/a	↓ (−49%)	n/a	n/a
Quinidine, 1000–1500 mg, oral (both steady‐state and not steady‐state) 76	PPK: n = 60, age 65 years, 46M/14FSubgroup with HF: n = 41, NYHA, age and M/F n/a	Yes	Yes	n/a	n/a	n/a	n/a	n/a	↓e (−46%)	n/a	n/a
Quinidine, 400 mg, oral and i.v. 65	HF: n = 8, NYHA II‐IV, age 60 ± 13 years, 4M/4FC: n = 10, age 54 ± 12 years, 6M/4F	No	No	→	→	n/a	↑ (+127%)	↓ (−34%)	↓ (−32%)	→	n/a
Quinidine, 600–840 mg, oral and i.m. 45	PPK: n = 39, age and M/F n/a HF subgroup: n = 20, NYHA, age and M/F n/a	n/a	n/a	n/a	n/a	n/a	n/a	↓f (−72%)	n/a	→	n/a
Quinidine, dose 100–2000 mg, oral 46	HF: n = 8, NYHA, age and M/F n/aC: n = 9, age and M/F n/a	No	No	n/a	n/a	→	n/a	n/a	n/a	→	n/a

AUC, area under the curve; C: controls; CL, clearance; C _max, maximum plasma/serum concentration; C _ss, concentration at steady state; F, bioavailability; F, female; HF, patients with heart failure; M, male; n/a not available/reported; NYHA, New York Heart Association functional class; PPK, population pharmacokinetics study; T _max, time to reach the maximum plasma/serum concentration; t _1/2, elimination half‐life; V_D, volume of distribution

^* , significant; ↑, significantly increased; ↓, significantly decreased; →, not statistically different;

^{a 15}N₂‐cibenzoline;

^b Sample size calculation performed;

^c No significant effect of heart failure on miscellaneous metabolic clearance (CL₀);

^d Plasma procaine half‐life assessed in vitro;

^e Severe heart failure or liver failure;

^f No statistical analysis performed