A pharmacokinetic study of digoxin in the horse

Journal of Veterinary Pharmacology and Therapeutics - Tập 6 Số 3 - Trang 163-172 - 1983
Gordon W. Brumbaugh1, William P. Thomas2, Lynda Enos1, Jun Kaneko3
1*Veterinary Medical Teaching Hospital, University of California, Davis, U.S.A
2†Departments of Veterinary Medicine, University of California, Davis, U.S.A
3‡Veterinary Clinical Pathology, University of California, Davis, U.S.A

Tóm tắt

Digoxin was administered orally and intravenously to seven healthy adult mares and geldings in two separate trials. At a dose of 44 μg digoxin/kg body weight, the oral study was characterized by an absorption phase with a mean (± 1 standard deviation) peak serum digoxin concentration of 2.21 ng/ml (± 0.45) at a mean of 2.29 h (± 1.52) after administration. A second rise in serum digoxin concentration started about 6–8 h after administration and extended to about 20 h after administration. The mean bioavailability (F) was 23.38% (± 5.96).

At a dose of 22 μg digoxin/kg body weight, the intravenous study was characterized by a two‐compartment model with the following mean pharmacokinetic measurements: distribution rate constant (α), 1.391 h‐1 (± 0.1909); zero‐time serum digoxin concentration determined from the distribution phase (A), 21.247 ng/ml (± 5.6614); elimination rate constant (β), 0.0409 h‐1 (± 0.0069); zero‐time serum digoxin concentration determined from the elimination phase (B), 3.82 ng/ml (± 0.433); apparent specific volume of distribution uncorrected for protein binding (Vdβ), 5.003 1/kg (± 0.5177). The mean β corresponded to a biological half‐life (t1/2 ±) of 16.9 h.

Based upon results of this study, theoretically achievable steady‐state serum digoxin concentrations were calculated for maintenance doses given by oral and intravenous routes of administration with appropriate two‐compartment, multiple‐dose formulae. Loading doses were also calculated for each route. It is the opinion of the authors that the oral route of administration of digoxin is effective in the horse and may preclude the potential risks posed by the high serum digoxin concentrations immediately following intravenous administration.

Từ khóa


Tài liệu tham khảo

Adams II.R., 1982, Veterinary Pharmacology and Therapeutics, 435

Barr I., 1972, Correlation of the electro‐physiologic action of digoxin with serum digoxin concentration, Journal of Pharmacology and Experimental Therapeutics, 180, 710

Beck A.M.(1969)Digoxin therapy and toxicity in dogs.Proceedings of the 36th Annual Meeting of the American Animal Hospital Association 23–30.

10.1161/01.CIR.45.1.20

Brumbaugh G.W., 1982, Medical management of congestive heart failure in a horse, Journal of the American Veterinary Medical Association, 180, 878

Button C., 1980, Digoxin pharmacokinetics, bio‐availability, efficacy, and dosage regimens in the horse, American Journal of Veterinary Research, 41, 1388

10.1136/bmj.3.5720.429

DeRick A., 1978, Plasma concentrations of digoxin and digitoxin during digitalization of healthy dogs and dogs with cardiac failure, American Journal of Veterinary Research, 39, 811

Detweiler D.K., 1977, Congestive heart failure in dogs: therapeutic concepts, Journal of the American Veterinary Medical Association, 171, 106

10.1097/00000441-196806000-00006

10.7326/0003-4819-79-2-229

10.1136/bmj.3.5720.427

10.1016/S0034-5288(18)33483-0

Fregin G.F., 1982, Equine Medicine and Surgery, 645

Gibaldi M., 1975, Pharmacokinetics.

Gross D.R., 1977, Congestive heart failure associated with congenital aortic valvular insufficiency in a horse, Southwestern Veterinarian, 30, 27

Hoffman B.F., 1980, The Pharmacological Basis of Therapeutics, 729

10.1016/0002-9343(75)90116-3

Pedersoli W.M., 1978, Pharmacokinetics of digoxin in the horse, Journal of Equine Medicine and Surgery, 2, 384

Pedersoli W.M., 1981, Pharmacokinetics of a single, orally administered dose of digoxin in horses, American Journal of Veterinary Research, 42, 1412

10.1002/jps.2600570123

Sams R., 1978, Pharmacokinetic and metabolic considerations as they apply to clinical pharmacology, 17

10.1056/NEJM196911272812203

10.1172/JCI106457

10.1016/S0140-6736(73)91010-6

10.1016/S0091-0279(78)50032-4