. 2020 Jul 27;10:12457. doi: 10.1038/s41598-020-69326-y

Table 4.

Summary of study designs used for pharmacokinetic analysis of digoxin.

Study	Study design	Number of subjects	Pharmacokinetic sampling	Dose regimen of digoxin	Identity and manufacturer of digoxin
Trial I⁵⁸	Reference period: digoxin 0.5 mg + midazolam 2 mg p.o. + midazolam 1 mg i.v. + tolbutamide 125 mg + caffeine 150 mg + omeprazole 20 mg + dextromethorphan 30 mg Test period: as above + ethanol (up to 0.7 ‰ C_max)	16 healthy Caucasian subjects (male = 8; female = 8)	Plasma (28 samples): -0:15 h predose, and postdose at 0:08, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:05, 2:08, 2:20, 2:30, 2:45, 3:00, 3:30, 4:00, 4:30, 5:00, 6:00, 8:00, 10:00, 12:00, 14:00, 16:00, 18:00 and 24:00 h Urine (6 collection interval): Predose, 0–6 h 6–10 h, 10–14 h, 14-18 h and 18-24 h	Single dose (2 tablets)	Digacin 0.25 mg Mibe GmbH Arzneimittel, Brehna, Germany
Trial II⁵²	Reference period: digoxin 0.5 mg Test period: digoxin 0.5 mg + adefovir 10 mg + metformin 500 mg + pitavastatin 2 mg + sitagliptin 100 mg	24 healthy Caucasian subjects (Male = 10; Female = 14)	Plasma (19 samples): -0:15 h predose, and postdose at 0:15, 0:30, 0:45, 1:00, 1:20, 1:40, 2:00, 2:20, 2:40, 3:00, 3:30, 4:00, 5:00, 6:00, 8:00, 12:00, 16:00 and 24:00 h Urine (6 collection interval): Predose, 0–4 h, 4–8 h, 8–12 h, 12–16 h and 16–24 h	Single dose (2 tablets)	Digacin 0.25 mg Mibe GmbH Arzneimittel, Brehna, Germany

Study

Study design

Number of subjects

Pharmacokinetic sampling

Dose regimen of digoxin

Identity and manufacturer of digoxin

Trial I⁵⁸

Reference period: digoxin 0.5 mg + midazolam 2 mg p.o. + midazolam 1 mg i.v. + tolbutamide 125 mg + caffeine 150 mg + omeprazole 20 mg + dextromethorphan 30 mg

Test period: as above + ethanol (up to 0.7 ‰ C_max)

16 healthy Caucasian subjects (male = 8; female = 8)

Plasma (28 samples): -0:15 h predose, and postdose at 0:08, 0:20, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:05, 2:08, 2:20, 2:30, 2:45, 3:00, 3:30, 4:00, 4:30, 5:00, 6:00, 8:00, 10:00, 12:00, 14:00, 16:00, 18:00 and 24:00 h

Urine (6 collection interval): Predose, 0–6 h 6–10 h, 10–14 h, 14-18 h and 18-24 h

Single dose (2 tablets)

Digacin 0.25 mg

Mibe GmbH Arzneimittel, Brehna, Germany

Trial II⁵²

Reference period: digoxin 0.5 mg

Test period: digoxin 0.5 mg + adefovir 10 mg + metformin 500 mg + pitavastatin 2 mg + sitagliptin 100 mg

24 healthy Caucasian subjects (Male = 10; Female = 14)

Plasma (19 samples): -0:15 h predose, and postdose at 0:15, 0:30, 0:45, 1:00, 1:20, 1:40, 2:00, 2:20, 2:40, 3:00, 3:30, 4:00, 5:00, 6:00, 8:00, 12:00, 16:00 and 24:00 h

Urine (6 collection interval): Predose, 0–4 h, 4–8 h, 8–12 h, 12–16 h and 16–24 h

Single dose (2 tablets)

Digacin 0.25 mg

Mibe GmbH Arzneimittel, Brehna, Germany

C_max, maximal observed plasma concentration.