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April 9, 1973, Vol 224, No. 2 >
ARTICLE | April 9, 1973

Equivalence Lack in Digoxin Plasma Levels FREE

John G. Wagner, PhD; Marianne Christensen; Ermelinda Sakmar; Donald Blair, MD; James D. Yates, MD; Park W. Willis, III, MD; Allen J. Sedman; Roger G. Stoll, PhD
[+] Author Affiliations

Reprint requests to Upjohn Center for Clinical Pharmacology, University of Michigan, Ann Arbor 48104 (Dr. Wagner).


JAMA. 1973;224(2):199-204. doi:10.1001/jama.1973.03220150013004
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Article
References

In an eight-subject two-way crossover study, 0.5-mg oral doses of digoxin were administered as two 0.25-mg tablets made by two different manufacturers. Treatment "B" yielded average peak plasma levels and areas under the curves that were 59% and 55%, respectively, of those attained following treatment "A". Two of the eight subjects also received the same dose in 5% dextrose both orally and by constant rate intravenous infusion during a one-hour period. Average peaks were 4.19, 3.76, 1.46, and 0.70 ng/ml following the intravenous infusion, solution orally, treatment A (tablet) orally, and treatment B (tablet) orally, respectively. Relative areas under the curves were 100%, 80.2%, 56.7%, and 30.7% for the treatments in the same order.

REFERENCES

1 +
Manninen V, Melin J, Härtel G:  Serum-digoxin concentrations during treatment with different preparations . Lancet 2:934-935, 1971;.
2 +
Lindenbaum J, et al:  Variation in biologic availability of digoxin from four preparations . N Engl J Med 285:1344-1347, 1971;.
3 +
Vitti TG, Banes D, Byers TE:  Bioavailability of digoxin . N Engl J Med 285:1433-1434, 1971;.
4 +
Hibble AG, Isaac P, Grahame-Smith DG:  Bioavailability of digoxin . Lancet 2:90-91, 1972;.
5 +
Shaw TRD, Howard MR, Hamer J:  Variation in the biological availability of digoxin . Lancet 2:303-307, 1972;.
6 +
 The bioavailability of digoxin , editorial. Lancet 2:311-312, 1972;.
7 +
Harris PA, Riegelman S:  Influence of the route of administration on the area under the plasma concentration time curve . J Pharm Sci 58:71-75, 1969;.
8 +
Stoll RG:  Specificity of the digoxin radioimmunoassay procedure . Res Com Chem Path Pharmacol 4:503-510, 1972;.
9 +
Marcus FI, Kapadia GJ, Kapadia GG:  The metabolism of digoxin in normal subjects . J Pharmacol Exp Ther 145:203-209, 1964;.
10 +
Wagner JG: Biopharmaceutics and Relevant Pharmacokinetics . Hamilton, Ill, Drug Intelligence Publications, 1972;, p 112.
11 +
Wells D, Katzung B, Myers FH:  Spectrofluorometric analysis of cardiotonic steroids . J Pharm Pharmacol 13:389-395, 1961;.
12 +
Feldmann EG:  Drug product selection-freedom with responsibility . J Am Pharm Assoc 12:368-374, 1972;.
13 +
Guidelines for Biopharmaceutical Studies in Man , APhA Academy of Pharmaceutical Sciences. Washington, D.C., American Pharmaceutical Association, 1972;, p 10.
14 +
Doherty JE, et al:  Tritiated digoxin: XIV. Enterohepatic circulation, absorption, and excretion studies in human volunteers . Circulation 42:867-873, 1970;.
15 +
Doherty JE:  The clinical pharmacology of digitalis glycosides: A review . Am J Med Sci 255:382-414, 1968;.
16 +
Chiou WL:  A simple equation to estimate the fraction of drug remaining in the body after an intravenous injection . J Pharm Pharmacol 34:342-343, 1972;.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Manninen V, Melin J, Härtel G:  Serum-digoxin concentrations during treatment with different preparations . Lancet 2:934-935, 1971;.
2 +
Lindenbaum J, et al:  Variation in biologic availability of digoxin from four preparations . N Engl J Med 285:1344-1347, 1971;.
3 +
Vitti TG, Banes D, Byers TE:  Bioavailability of digoxin . N Engl J Med 285:1433-1434, 1971;.
4 +
Hibble AG, Isaac P, Grahame-Smith DG:  Bioavailability of digoxin . Lancet 2:90-91, 1972;.
5 +
Shaw TRD, Howard MR, Hamer J:  Variation in the biological availability of digoxin . Lancet 2:303-307, 1972;.
6 +
 The bioavailability of digoxin , editorial. Lancet 2:311-312, 1972;.
7 +
Harris PA, Riegelman S:  Influence of the route of administration on the area under the plasma concentration time curve . J Pharm Sci 58:71-75, 1969;.
8 +
Stoll RG:  Specificity of the digoxin radioimmunoassay procedure . Res Com Chem Path Pharmacol 4:503-510, 1972;.
9 +
Marcus FI, Kapadia GJ, Kapadia GG:  The metabolism of digoxin in normal subjects . J Pharmacol Exp Ther 145:203-209, 1964;.
10 +
Wagner JG: Biopharmaceutics and Relevant Pharmacokinetics . Hamilton, Ill, Drug Intelligence Publications, 1972;, p 112.
11 +
Wells D, Katzung B, Myers FH:  Spectrofluorometric analysis of cardiotonic steroids . J Pharm Pharmacol 13:389-395, 1961;.
12 +
Feldmann EG:  Drug product selection-freedom with responsibility . J Am Pharm Assoc 12:368-374, 1972;.
13 +
Guidelines for Biopharmaceutical Studies in Man , APhA Academy of Pharmaceutical Sciences. Washington, D.C., American Pharmaceutical Association, 1972;, p 10.
14 +
Doherty JE, et al:  Tritiated digoxin: XIV. Enterohepatic circulation, absorption, and excretion studies in human volunteers . Circulation 42:867-873, 1970;.
15 +
Doherty JE:  The clinical pharmacology of digitalis glycosides: A review . Am J Med Sci 255:382-414, 1968;.
16 +
Chiou WL:  A simple equation to estimate the fraction of drug remaining in the body after an intravenous injection . J Pharm Pharmacol 34:342-343, 1972;.

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