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Pharmacological profiles of intravenously and subcutaneously administered fentanyl in the rabbit (Oryctolagus
Vanessa Bettembourg1, Lena Olsén1, Anneli Rydén1
1Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Agricultural Sciences, Uppsala, Sweden.
Objective:
To measure the bioavailability, maximal plasma concentration (Cmax) and half-life (t½) of fentanyl in rabbits after intravenous (IV) and subcutaneous (SC) administration. Secondary aims were to investigate behavioural effects and faeces production.
Study Design:
Randomized, experimental, crossover study.
Animals:
A group of six male New Zealand White rabbits, Crl:KBL(NZW), aged 5-6 months and weighing 2.9-3.7 kg.
Methods:
Fentanyl 15 μg kg-1 was administered IV and SC to rabbits with a 14 day washout period. Plasma was sampled at 2 (IV), 5, 10, 15, 30, 60, 90, 120 (IV + SC), 300 (SC) and 390 (SC) minutes and analysed by liquid chromatography-mass spectrometry. Sedation was scored from 0-3, 3 being most sedated, 10 and 45 minutes after administration by an assessor blinded to treatment. Oxygen was supplemented if the haemoglobin oxygen saturation (SpO2) was <90%. After the experiment, faeces and urine were weighed. Data are presented as mean ± standard deviation or median (range).
Results:
Bioavailability for fentanyl after SC administration was 47% ± 16% and 50% (27%-68%). The t½ for fentanyl after IV and SC administration was 65 ± 11 and 275 ± 16 minutes, respectively. The Cmax of fentanyl after SC injection was 0.55 ± 0.17 ng mL-1 and the time to maximal concentration (Tmax) was 15 (15-68) minutes. Median sedation score at 10 minutes was higher (p = 0.014) after IV than after SC administration (3 and 1, respectively). After IV administration, but not SC administration, 5/6 rabbits became recumbent and 2/6 rabbits required oxygen. There was no statistically significant difference in faecal/urinary output between groups.
Conclusions And Clinical Relevance:
Fentanyl administered SC as the sole drug to conscious rabbits resulted in variable plasma concentrations substantially lower than after IV administration. Supplemental oxygen should be available whenever fentanyl is administered.
