Enantioselective pharmacokinetics of racemic carprofen in New Zealand white rabbits

Abstract

The enantioselective pharmacokinetics of single dose (2 mg/kg) racemic carprofen (CPF) were evaluated in adult New Zealand white rabbits after intravenous (i.v.) and subcutaneous (s.c.) dose. Six rabbits were utilized in a two-way randomized crossover study and serial blood samples were collected. Plasma CPF concentrations were determined by high-performance liquid chromatography. After i.v. and s.c. racemic CPF administration, plasma concentration-time curves were best described by a two-compartment open model and a one-compartment model, respectively. The S(+) CPF enantiomer predominated in plasma following both routes of administration. Mean observed clearance of R(-)-CPF (82.17 +/- 13.70 mL/h.kg) was more rapid than for S(+)-CPF (27.92 +/- 7.07 mL/h.kg; P < 0.001). T(1/2)lambda z was shorter for R(-)-CPF than S(+)-CPF after both i.v. (1.03 and 2.99 h, respectively) and s.c. (1.94 and 4.14 h, respectively) dosing. Mean AUC(0-->infinity) ratios for R(-):S(+)-CPF were approximately 1:3 for both routes of administration. Mean residence time of R(-)-CPF was shorter than of S(+)-CPF (1.06 +/- 0.29 h, 3.45 +/- 0.50 h; P < 0.001) and R(-)- and S(+)-CPF volumes of distribution at steady state were 85.00 +/- 14.42 and 94.39 +/- 18.66 mL/kg, respectively after i.v. administration. The mean s.c. bioavailability [F (%)] for both R(-)- and S(+)-CPF was high, 94.4 +/- 22.8 and 91.0 +/- 35.7%, respectively.

Pharmacokinetic Appraisal of Carprofen Delivery from Intra-Articular Nanoparticles: A Population Modeling Approach in Rabbits

“…As previously reported [12,24,25], CP disposition was best described by a two-compartment model. The steady-state distribution volume (Vss = 0.1126 L/kg mean live bodyweight) was in line with other results in rabbits [26], dogs 0.1192 L/kg [24] or cats (0.1506 L/kg) [27]. Considering a total body-water of 0.61 L/kg in live rabbits [28], the low Vss values suggest that carprofen is mainly confined in plasma according to its high protein-binding [29] as other NSAIDs [2].…”

Swine as the Animal Model for Testing New Formulations of Anti-Inflammatory Drugs: Carprofen Pharmacokinetics and Bioavailability of the Intramuscular Route

“…In line with other animal species [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], the apparent distribution volume (Vss = Vc + VP = 9.62 L or 0.306 L/kg for a mean bodyweight of 31.5 kg) was lower than the total body water (0.63 L/kg) [ 48 ], due to the fact that CP is mainly confined in plasma according to its high protein binding as other NSAIDs [ 49 ].…”

“…The swine model has been used in pharmacokinetic (PK) studies of different drugs to further predict human PK through allometric models. Numerous CP pharmacokinetic studies have been conducted in various species: horses [ 18 , 19 ], donkeys [ 20 ], calves [ 21 , 22 ], sheep [ 23 ], rabbits [ 24 , 25 ], vultures [ 26 ], humans [ 27 ], dogs [ 28 , 29 ] and cats [ 30 , 31 ]; however, very few CP PK studies have been published in swine [ 32 ], probably because its use in this specie is uncommon. Moreover, CP have never been administered by the intramuscular route in this species.…”

Anesthesia, Analgesia, and Sedation of Small Mammals

“…Very little work has been done to date evaluating this drug in exotic animal species. 46 The authors have used 1 to 4 mg/kg PO, SC, and IM q12-24h shortterm (<7 days) in many small mammal species. 101 Postoperative food and water consumption were improved when rats were administered 5 mg/kg SC but not PO, suggesting that higher doses may be necessary with PO dosing.…”