Table 1.

Pharmacokinetic studies of positive inotropes and vasopressors 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
Digoxin, 0.75 mg, oral 37	HF: n = 12, NYHA n/a, age 61 ± 4 years, 10M/2FC: n = 9, age 60 ± 16 years, 7M/2F	No	n/a	n/a	↓ (−36%)	n/a	→	n/a	→	n/a	→
Digoxin, 0.19 mg day −1 , oral, 69	PPK: n = 385, age 60 ± 13 years, 207M/178F HF subgroup: n = 77, NYHA and age n/a, 43M/34F	Yes	No	n/a	n/a	n/a	n/a	n/a	↓ (−19%)	n/a	n/a
Digoxin, 0.21 mg day −1 , oral 49	HF: n = 10, NYHA n/a, age 76 ± 5 years, M/F n/aC: n = 9, age 77 ± 11 years, M/F n/a	Yes	n/a	n/a	n/a	↑ (+40%)	n/a	n/a	↓ (−32%)	n/a	n/a
Digoxin, n/a, oral 81	PPK: n = 106, age n/a, 43M/63F HF subgroup: n = 14, NYHA, age and M/F n/a	Yes	No	n/a	n/a	n/a	n/a	n/a	→	n/a	n/a
Digoxin, 3.8 μg kg −1 day −1 , oral 91	PPK: n = 94, age 74 ± 6 years, 60M/34F HF subgroup: n = 41, NYHA, age and M/F n/a	No	n/a	n/a	n/a	n/a	n/a	n/a	↓ (−6%)	n/a	n/a
Digoxin, n/a, oral 92	PPK: n = 122, age 75 ± 8 years, M/F n/a HF subgroup: n, NYHA, age and M/F n/a	Yes	No	n/a	n/a	n/a	n/a	↓ (−10%)	↓ (−10%)	n/a	n/a
Enoximone, 1–2 mg kg −1 (75 mg in controls), oral 50	HF: n = 7, NYHA III‐IV, age 51 years, M/F n/aC: n = 2, age and M/F n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	↓a (−58%)	↑a (+21%)	n/a
Adrenaline, 1‐h i.v. infusion b 70	HF: n = 42, NYHA III‐IV, age 50 ± 1 years, 39M/3FC: n = 31, age 41 ± 5 years, 31M/0F	n/a	n/a	n/a	n/a	↑ (+49%)	n/a	n/a	↓ (−34%)	n/a	n/a
Noradrenaline, 1‐h i.v. infusion c 70	HF: n = 42, NYHA III‐IV, age 50 ± 1 years, 39M/3FC: n = 31, age 41 ± 5 years, 31M/0F	n/a	n/a	n/a	n/a	↑ (+121%)	n/a	n/a	↓ (−26%)	n/a	n/a
Noradrenaline, 0.5‐h i.v. infusion d 71	HF: n = 7, NYHA III‐IV, age 49 ± 3 years, 6M/1FC: n = 6, age 38 ± 3 years, 6M/0F	n/a	n/a	n/a	n/a	↑ (+204%)	n/a	n/a	↓ (−43%)	n/a	n/a
Noradrenaline, 0.5‐h i.v. infusion d 72	HF: n = 8, NYHA III‐IV, age 56 ± 4 years, 8M/0FC: n = 9, age 38 ± 2 years, 9M/0F	n/a	n/a	n/a	n/a	↑ (+111%)	n/a	n/a	↓ (−56%)	n/a	n/a
Isoprenaline, 0.5‐h i.v. infusion e 72	HF: n = 8, NYHA III‐IV, age 56 ± 4 years, 8M/0FC: n = 9, age 38 ± 2 years, 9M/0F	n/a	n/a	n/a	n/a	n/a	n/a	n/a	↓ (−43%)	n/a	n/a
Levosimendan, 0.50 mg, oral f and i.v. g 73	HF: n = 8, NYHA II, age 54 years, 8M/0FC: n = 8, age 54 years, 8M/0F	No	No	→	→a	n/a	→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 no statistical analysis performed;

^b l‐[N‐methyl‐³H] adrenaline (0.5–1.0 μCi min⁻¹);

^c l‐[7‐³H] noradrenaline (0.5–1.0 μCi min⁻¹);

^d l‐[ring‐2,3,6‐³H] noradrenaline (15 μCi m⁻² over 5 min followed by 1.05 μCi min⁻¹ m⁻²);

^e d,l‐[7‐³H(N)]isoprenaline (15 μCi m⁻² over 5 min followed by 1.05 μCi min⁻¹ m⁻²);

^{f 13}C¹⁵N‐labelled;

^{g 14}C‐labelled