title: Quinidine administration increases steady state serum digoxin concentration in horses.
abstract: The aim of this study was to determine if quinidine administration increases steady state serum digoxin concentration in horses. Digoxin (0.01 mg/kg q. 12 h per os) was administered to 6 horses for 7 days. Steady state was confirmed by identifying statistically indistinguishable peak and trough serum digoxin concentrations on Days 4, 5, and 6. On Day 6, serum digoxin concentration was measured at baseline and 0.25, 0.5, 1, 2, 4, 6, 8 and 12 h after digoxin administration. On Day 7, quinidine (20 g at baseline and 10 g at 2, 4 and 6 h) was administered per os and serum digoxin concentration was measured at the same time intervals. Creatinine and renal digoxin clearances were measured on Days 6 and 7. Results indicated that there was approximately a doubling of serum digoxin concentration (from mean +/- s.d. 2.57 +/- 0.96 ng/ml at baseline to 4.28 +/- 1.31 at 15 min and 5.98 +/- 1.21 ng/ml at 30 min) after starting the administration of quinidine. This elevation persisted for the 12 h after starting quinidine administration. Renal digoxin and endogenous creatinine clearances decreased but the decrease in digoxin clearance was greater. Serum quinidine concentration achieved the therapeutic range (2-6 micrograms/ml) in 5 of the 6 horses. In summary, similar to findings in other species, quinidine administration increases steady state serum digoxin concentration in horses and this occurs, at least in part, due to a decrease in renal digoxin clearance. Some of the decrease in renal clearance is due to decreased glomerular filtration which is dissimilar to findings in other species.
authors.affiliation: Veterinary Medical Teaching Hospital, University of California, Davis, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Parraga
authors.forename: M D
authors.initials: MD
authors.lastname: Kittleson
authors.forename: C M
authors.initials: CM
authors.lastname: Drake
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000494:pharmacology*; D003404:Creatinine / Q000378:metabolism; D004077:Digoxin / Q000097:blood* / Q000493:pharmacokinetics; D004569:Electroencephalography / Q000662:veterinary; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006736:Horses / Q000097:blood* / Q000502:physiology; D007668:Kidney / Q000196:embryology / Q000502:physiology; D011802:Quinidine / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D004077:Digoxin; D003404:Creatinine; D011802:Quinidine