Table 6.

Pharmacokinetic studies of other classes of drugs 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
Theophylline, n/a, i.v. 47	PPK: n = 57, age n/a, 27M/30F HF subgroup: n = 3, NYHA n/a, age 63 ± 8 years, 2M/1F	n/a	No	n/a	n/a	n/a	n/a	→	↓ (−43%)	n/a	n/a
Theophylline, n/a, oral and i.v. 78	PPK: n = 204, age 60 years, 113M/91FHF subgroup: n = 24, NYHA, age and M/F n/a	No	No	n/a	n/a	n/a	n/a	n/a	↓ (−25%)	n/a	n/a
Theophylline, 700 mg, oral 79	HF: n = 11, NYHA II‐III, age 77 years, 5M/6FC: n = 15, age 75 years, 8M/7F	n/a	n/a	n/a	→	n/a	↑ (+81%)	→	↓a (−69%)	↑a (+267%)	n/a
Theophylline, n/a, oral 80	HF: n = 16, NYHA II‐IV, age 67 ± 9 years, 11M/5FC: n = 16, age 61 ± 10 years, 13M/3F	No	No	n/a	n/a	n/a	n/a	n/a	↓ (−43%)	n/a	n/a
Theophylline, 208 mg, i.v. 68	HF: n = 50, NYHA III‐IV age 20–72 years, 30M/20FC: n = 20, age and M/F n/a	n/a	n/a	n/a	n/a	n/a	n/a	→	↓ (−62%)	↑ (+84%)	n/a
Theophylline, n/a, i.v. 48	PPK: n = 200, age n/a, 95M/105F HF subgroup: n = 51, NYHA, age and M/F n/a	Yes	Yes	n/a	n/a	n/a	n/a	n/a	↓b (−37%)	n/a	n/a
Conivaptan, 20–40 mg, oral and i.v. 89	HF: n = 58, NYHA, age and M/F n/aC: n = 145, age and M/F n/a	Yes	No	n/a	→	→	n/a	n/a	→	→	→
Tolvaptan, 5–240 mg, oral 94	PPK: n = 745, age 61 ± 7 years, 484M/261FHF subgroup: n = 628, NYHA I‐IV, age 64 ± 13 years, M/F n/a	n/a	Yes	n/a	n/a	n/a	n/a	↓ (−40%)c (−49%)d	↓ (−42%)c (−55%)d	n/a	n/a
Dabigatran, 110–150 mg, oral 95	PPK: n = 9522, age 71 ± 9 years, 6190M/3332FHF subgroup: n = 3039, NYHA I‐IV, age and M/F n/a	Yes	n/a	n/a	n/a	n/a	n/a	→	↓ (−7%)e	n/a	↑ (+7%)e
Darbopoetin, 0.75–5 s μg kg −1 , s.c. and i.v. 90	HF: n = 33, NYHA II‐IV, age n/a, 17M/16FC: n = 30, age n/a, 17M/13F	Yes	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 Significant difference in males only;

^b Moderate–severe heart failure vs. controls and subjects with mild heart failure;

^c NYHA class I‐II;

^d NYHA class III‐IV;

^e NYHA class II‐IV vs. controls and subjects with NYHA class I