The effect of cardiopulmonary bypass on the turnover rates of digoxin in the serum of dogs

Doherty, James E.; Hara, Masauki; Lincoln, Beth; Perkins, William H.

doi:10.1016/0002-8703(62)90153-9

Cited by 13 publications

(5 citation statements)

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“…For digoxin the half-lives have been determined in several species using observation periods long enough to yield true elimination rates: rats 13.5 h (Abshagen et al, 1972) and 9-5 h (Kikuchi & Okita, 1967); dogs 27-28 h (range 20-63 h) (Barr et al, 1972;Doherty et al, 1962), cats 27 h (Okita, 1967; no data on the observation length). For guinea-pigs, Kikuchi & Okita (1967) reported a digoxin half-life of 16 h, without giving information on the observation period.…”

Section: Discussionmentioning

confidence: 99%

“…It should be noted that there is good evidence suggesting that the elimination kinetics of cardiac glycosides after both single and maintenance administration, as well as on different dose schedules, do not differ from each other (Barr et al, 1972;Doherty et al, 1962;Hundeshagen et al, 1968;Lukas, 1971Lukas, , 1973aSelden & Smith, 1972, 1973Jelliffe, 1967).…”

Section: Discussionmentioning

confidence: 99%

“…In spite of fundamental contributions by numerous investigators (Abshagen, von Bergmann & Rietbrock, 1972;Barr et al, 1972;Caldwell & Greenberger, 1971 ;Doherty et al, 1962;Doherty & Perkins, 1966;Dutta, Marks & Smith, 1963;Fischer, Sjoerdsma & Johnson, 1952;Gadke, 1969;Harrison et al, 1966;Katzung & Meyers, 1965;Okita, 1967Okita, , 1969Selden & Smith, 1972, 1973, the kinetics of ouabain, digoxin and digitoxin in laboratory animals remain subject to debate. Particularly, a considerable discrepancy between very short elimination half-lives determined in blood and very slow excretion rates of cardiac glycosides is evident in the literature (Dutta et al, 1963;Gadke, 1969;Geiling et al, 1950;Ingwersen, 1974;Lullmann & Schaum, 1968).…”

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Pharmacokinetics of tritiated ouabain, digoxin and digitoxin in guinea‐pigs

Proppe

1975

Clin Exp Pharma Physio

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1. Elimination rates of tritiated ouabain, digoxin and digitoxin after single intravenous administrations were investigated in guinea-pigs, the total radioactivity in whole blood being traced for a period of up to 2 weeks. 2. In the initial rapid phase of elimination between 2 and 30 min following intravenous glycoside administration, the concentration decline of radioactivity in the blood was found to be identical for the three glycosides investigated, this part of the elimination curve displaying a hyperbolic shape. 3. During this early elimination phase, rapid metabolic degradation and excretion of digoxin had already taken place. The maximum concentration of radioactivity in the bile was reached 4 min following intravenous administration of 3H-digoxin. The positive inotropic response occurred in the cat heart-lung preparation 1.5 min after intravenous injection of a therapeutic dose of digoxin, indicating a quick occupation of binding sites in the tissues. 4. The biological half-lives of tritiated ouabain, digoxin and digitoxin averaged 11 h, 2.5 days and 4.1 days, respectively, as determined by the terminal exponential elimination phase, in guinea-pigs. This terminal phase was attained 6-12, 7-24, and 24-48 h after administration of ouabain, digoxin and digitoxin, respectively. 5. The findings reveal that in guinea-pig, as has been demonstrated in man, the elimination rates of the three glycosides increase according to their hydrophobic properties. 6. The biological half-lives of tritiated ouabain, digoxin and digitoxin obtained in the guinea-pig closely resemble those found in healthy man.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Pharmacokinetics of tritiated ouabain, digoxin and digitoxin in guinea‐pigs

Proppe

1975

Clin Exp Pharma Physio

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“…Blood samples were obtained just before each daily dose and at 24 and 48 hours after the last intravenous dose of ouabain. All urine was collected for a period of 12 days, including the 9 days of ouabain administration and the 3 days subsequent to the last dose.…”

Section: Assay Methodsmentioning

confidence: 99%

Ouabain Pharmacokinetics in Dog and Man

1972

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SUMMARYThe pharmacokinetics of the relatively polar and rapidly acting cardiac glycoside ouabain (G-strophanthin) were studied in dogs and human subjects by the use of a newly devised radioimmunoassay technic. This method had high specificity and a sensitivity of less than 0.1 ng of ouabain per ml of plasma or urine. After administration of a single intravenous dose, the plasma ouabain concentration fell rapidly in both dogs and humans. After 7 hours, a phase of exponential decline was reached which had a half-life of 18 hours in dogs and 21 hours in normal human subjects. Repeated intravenous administration of ouabain to human subjects for 9 consecutive days resulted in the establishment of a plateau of plasma concentration and urinary excretion after 4-5 days, confirming plasma and urinary half-lives in the 19-24-hour range. The mean ratio of renal clearance of ouabain to that of creatinine was 0.81 in the human subjects. The plasma half-life of ouabain determined in these studies is in good agreement with previous observations of the half-life of dissipation of positive inotropy and of slowing of ventricular response to atrial fibrillation after ouabain administration.

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“…Previous studies with tritiated digoxin are utilized in these computations. [1][2][3][4][5][6][7][8][9][10][11][12][13] Methods Six male patients with biliary tract disease who were candidates for T-tube drainage postoperatively were selected for study. Clinical diagnoses …”

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confidence: 99%

Tritiated Digoxin

et al. 1970

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SUMMARYMetabolic turnover studies performed on six patients with surgically induced biliary fistula given tritiated digoxin reveal virtually all stool excretion of digoxin to be derived from bile. This establishes the relative lack of recycling of digoxin as an important factor in digoxin metabolism. This is probably related to its polar chemical structure and is a determinant of its clinical duration of action in human subjects. The amount of digoxin in the enterohepatic circulation (recycling) was calculated to be 6.5% of the administered dose and absolute absorption to be 85% in human subjects.Additional Indexing Words: Biliary fistula Digoxin, metabolism of T HE availability of 3H digoxin for experi--mental clinical use has made possible a number of meaningful studies during the last decade.1-17 These studies have outlined the serum tumover rates, serum half-time (the time required for one half of the radioactivity identified with the drug to disappear from the serum) and serum digoxin levels. The urinary and fecal excretion of digoxin was characterized, and the larger portion of the drug was found to be excreted unchanged in the urine.Comparative studies in patients given 3H digoxin by oral, intramuscular, and intravenous routes suggested that digoxin was more From the

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The effect of cardiopulmonary bypass on the turnover rates of digoxin in the serum of dogs

Cited by 13 publications

References 9 publications

Pharmacokinetics of tritiated ouabain, digoxin and digitoxin in guinea‐pigs

Pharmacokinetics of tritiated ouabain, digoxin and digitoxin in guinea‐pigs

Ouabain Pharmacokinetics in Dog and Man

Tritiated Digoxin

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