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The steady‐state pharmacokinetics and bioequivalence of carprofen administered orally and subcutaneously in dogs
Author(s) -
Clark T. P.,
Chieffo C.,
Huhn J. C.,
Nimz E. L.,
Wang C.,
Boy M. G.
Publication year - 2003
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1046/j.1365-2885.2003.00475.x
Subject(s) - bioequivalence , beagle , pharmacokinetics , carprofen , crossover study , confidence interval , oral administration , bioavailability , plasma concentration , geometric mean , pharmacology , medicine , area under the curve , chemistry , mathematics , placebo , alternative medicine , pathology , statistics
Eighteen male Beagle dogs were randomized to oral (p.o.) or subcutaneous (s.c.) carprofen administration in a two‐sequence, two‐period crossover design with a 10‐day washout between periods. Twenty‐five milligrams of carprofen was administered p.o. or s.c. every 12 h for 7 days. Plasma concentrations of carprofen collected after the first and last treatments were determined by high‐performance liquid chromatography. Carprofen concentration data were natural log transformed and geometric means were calculated for maximum plasma concentration ( C max ) and area under the plasma concentration–time curve ( AUC 0‐‐12 ) following the first dose and C max and AUC 0‐‐12 following administration of the last dose. Formulations were considered bioequivalent if the 90% confidence interval (CI) of the mean difference for each variable between formulations were within −20% and 25% of the oral formulation. The mean C max and AUC 0‐‐12 were 16.9 μ g/mL and 73.1 μ g · h/mL, respectively, following a single oral dose and 8.0 μ g/mL and 64.3 μ g · h/mL, respectively, following a single s.c. injection. The 90% CI for C max (−56.8 to −48.7%) was outside of the bioequivalence criteria whereas the 90% CI for AUC 0‐‐12 (−16.3 to −7.5%) was within the bioequivalence criteria. At steady‐state, the mean C max and AUC 0‐‐12 were 18.7 μ g/mL and 101.9 μ g · h/mL, respectively, following p.o. administration and 14.7 μ g/mL and 111.0 μ g · h/mL, respectively, following s.c. injection. The 90% CI was outside the bioequivalence criteria for C max (−30.8 to −10.8) but within the bioequivalence criteria for AUC 0‐‐12 (2.3–15.9%). The results of this study indicate that peak plasma concentrations of carprofen differ when administered p.o. and s.c., but that total drug exposure following a single dose and at steady‐state are bioequivalent.