Pharmacokinetics of carvedilol after intravenous and oral administration in conscious healthy dogs

Wendy G. Arsenault Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474.
present address is Southwest Florida Veterinary Cardiology, 27223 Barefoot Ln, Bonita Springs, FL 34135.

Search for other papers by Wendy G. Arsenault in
Current site
Google Scholar
PubMed
Close
 DVM
,
Dawn M. Boothe Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474.

Search for other papers by Dawn M. Boothe in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Sonya G. Gordon Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474.

Search for other papers by Sonya G. Gordon in
Current site
Google Scholar
PubMed
Close
 DVM, DVSc
,
Matthew W. Miller Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474.

Search for other papers by Matthew W. Miller in
Current site
Google Scholar
PubMed
Close
 DVM, MSc
,
Jeffrey R. Chalkley Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474.
Present address is Department of Clinical Science, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

Search for other papers by Jeffrey R. Chalkley in
Current site
Google Scholar
PubMed
Close
 DVM
, and
Ilona Petrikovics Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474.
Present address is 142 McAdory Hall, Auburn University, Auburn, AL 36849.

Search for other papers by Ilona Petrikovics in
Current site
Google Scholar
PubMed
Close
 PhD

Click on author name to view affiliation information

Abstract

Objective—To determine the pharmacokinetics of carvedilol administered IV and orally and determine the dose of carvedilol required to maintain plasma concentrations associated with anticipated therapeutic efficacy when administered orally to dogs.

Animals—8 healthy dogs.

Procedures—Blood samples were collected for 24 hours after single doses of carvedilol were administered IV (175 µg/kg) or PO (1.5 mg/kg) by use of a crossover nonrandomized design. Carvedilol concentrations were detected in plasma by use of high-performance liquid chromatography. Plasma drug concentration versus time curves were subjected to noncompartmental pharmacokinetic analysis.

Results—The median peak concentration (extrapolated) of carvedilol after IV administration was 476 ng/mL (range, 203 to 1,920 ng/mL), elimination half-life (t1/2) was 282 minutes (range, 19 to 1,021 minutes), and mean residence time (MRT) was 360 minutes (range, 19 to 819 minutes). Volume of distribution at steady state was 2.0 L/kg (range, 0.7 to 4.3 L/kg). After oral administration of carvedilol, the median peak concentration was 24 µg/mL (range, 9 to 173 µg/mL), time to maximum concentration was 90 minutes (range, 60 to 180 minutes), t1/2 was 82 minutes (range, 64 to 138 minutes), and MRT was 182 minutes (range, 112 to 254 minutes). Median bioavailability after oral administration of carvedilol was 2.1% (range, 0.4% to 54%).

Conclusions and Clinical Relevance—Although results suggested a 3-hour dosing interval on the basis of MRT, pharmacodynamic studies investigating the duration of β-adrenoreceptor blockade provide a more accurate basis for determining the dosing interval of carvedilol. (Am J Vet Res 2005;66:2172–2176)

Abstract

Objective—To determine the pharmacokinetics of carvedilol administered IV and orally and determine the dose of carvedilol required to maintain plasma concentrations associated with anticipated therapeutic efficacy when administered orally to dogs.

Animals—8 healthy dogs.

Procedures—Blood samples were collected for 24 hours after single doses of carvedilol were administered IV (175 µg/kg) or PO (1.5 mg/kg) by use of a crossover nonrandomized design. Carvedilol concentrations were detected in plasma by use of high-performance liquid chromatography. Plasma drug concentration versus time curves were subjected to noncompartmental pharmacokinetic analysis.

Results—The median peak concentration (extrapolated) of carvedilol after IV administration was 476 ng/mL (range, 203 to 1,920 ng/mL), elimination half-life (t1/2) was 282 minutes (range, 19 to 1,021 minutes), and mean residence time (MRT) was 360 minutes (range, 19 to 819 minutes). Volume of distribution at steady state was 2.0 L/kg (range, 0.7 to 4.3 L/kg). After oral administration of carvedilol, the median peak concentration was 24 µg/mL (range, 9 to 173 µg/mL), time to maximum concentration was 90 minutes (range, 60 to 180 minutes), t1/2 was 82 minutes (range, 64 to 138 minutes), and MRT was 182 minutes (range, 112 to 254 minutes). Median bioavailability after oral administration of carvedilol was 2.1% (range, 0.4% to 54%).

Conclusions and Clinical Relevance—Although results suggested a 3-hour dosing interval on the basis of MRT, pharmacodynamic studies investigating the duration of β-adrenoreceptor blockade provide a more accurate basis for determining the dosing interval of carvedilol. (Am J Vet Res 2005;66:2172–2176)

All Time Past Year Past 30 Days
Abstract Views 43 0 0
Full Text Views 392 307 30
PDF Downloads 135 82 8
Advertisement