Table 1.
Noncompartmental analysis of pharmacokinetic parameters after administration of fentanyl or buprenorphine via air chamber. Cmax, maximum plasma concentration; Tmax, time of maximum plasma concentration; T1/2, plasma elimination half-life; AUC 0→∞, area under the curve from time 0 extrapolated to infinity; AUMC 0→∞, area under the first moment curve from time 0 extrapolated to infinity; MRT 0→∞, mean residence time from time 0 extrapolated to infinity; Vd/F, volume of distribution; CL/F, clearance.
Fig 1.
Plasma concentration of fentanyl and buprenorphine after administration via air chamber. a Fentanyl plasma concentrations (ng/ml) at 5 (n = 10), 15 (n = 11), 30 (n = 8), 60 (n = 4), and 120 (n = 4) min after application of 0.2 mg/kg (egg weight) via air chamber are presented as individual data points and mean (line). b Buprenorphine plasma concentrations (ng/ml) at 15, 30, 60, and 120 min (n = 7 per time point) after application of 0.5 mg/kg (egg weight) via air chamber are presented as individual data points and mean (line).
Fig 2.
Correlation analysis of individual fentanyl und buprenorphine plasma concentrations and the dose administered per embryo at the time points examined after application via the air chamber.
a Pearson correlation analysis of fentanyl plasma concentration (ng/ml) at 5 (n = 10), 15 (n = 11), 30 (n = 8), 60 (n = 4), and 120 (n = 4) min after application of 0.2 mg/kg (egg weight) via the air chamber and individual calculated dose per embryo (mg/kg) is presented as individual data points and simple linear regression (line). b Pearson correlation analysis of buprenorphine plasma concentrations (ng/ml) at 15, 30, 60, and 120 min (n = 7 per time point) after application of 0.5 mg/kg (egg weight) via air chamber and individual calculated dose per embryo (mg/kg) is presented as individual data points and simple linear regression (line).
Fig 3.
Percent change in MAP and HR after mechanical stimulation with fentanyl.
ED17 embryos received a mechanical stimulus (Pinch/Touch) at different time points (15, 30, 60 min) after administration of NaCl or fentanyl. (a-c) Percent change from BL in MAP after Pinch and Touch. Values are shown as the mean ± SD. (d-f) Percent change in MAP over time. Values one min before and one min after Pinch are shown as the mean ± SD (shaded). (g-i) Percent change in HR over time. Values one min before and one min after Pinch are shown as the mean ± SD (shaded). Normally distributed data were analyzed by ordinary one-way ANOVA (a, b), non-normally distributed data by a Kruskal-Wallis test (c). A p-value of <0.01 was considered statistically significant.
Fig 4.
Percent change in MAP and HR after mechanical stimulus with buprenorphine.
ED17 embryos received a mechanical stimulus (Pinch/Touch) at different time points (15, 30, 60 min) after administration of NaCl or buprenorphine. (a-c) Percent change in MAP after Pinch and Touch. Values are shown as the mean ± SD. (d-f) Percent change in MAP over time. (g-i) Percent change in HR over time. Values one min before and one min after Pinch are shown as the mean ± SD (shaded).
Table 2.
Effects of fentanyl and buprenorphine on cardiovascular parameters. Systolic (SAP), diastolic (DAP), mean arterial pressure (MAP), and heart rate (HR) of chicken embryos on ED17 at 15, 30, and 60 min after application of NaCl, fentanyl, or buprenorphine. Values are shown as the mean ± SD. Normally distributed data (HR, MAP, DAP) were analyzed using ordinary one-way ANOVA. For nonparametric data (SAP) a Kruskal-Wallis test was performed. Superscripts within the HR row indicate significant differences between groups (p < 0.05). Significant differences in HR were observed between Fentanyl 15 min and Fentanyl 30 min.
Fig 5.
Effects of fentanyl and buprenorphine on behavioral parameters.
Number of body movements (a, b) and wide beak openings (c, d) of ED17 chicken embryos at 15, 30 and 60 min after injection of NaCl (a-d), fentanyl (a, c) and buprenorphine (b, d) during one min before (BL) and one min after Pinch. The absolute number of body movements and wide beak openings per embryo and their calculated means are shown. (c, d) Significances shown result from the comparison of the total number of embryos per group that showed wide beak opening. Data that reached significance in the Fisher-Freeman-Halton test were further analyzed using a post-hoc Fisher test with Bonferroni correction for multiple testing.
Fig 6.
A comparison: Percent Change in MAP after Pinch with fentanyl/buprenorphine (ED17) and lidocaine (ED18).
ED17 embryos that received a Pinch 15 min after application of NaCl, fentanyl and buprenorphine compared to ED18 embryos being pinched after injection of NaCl and lidocaine. The percent change from BL in MAP after Pinch is presented. Values are shown as the mean ± SD. Infiltration anesthesia by injection of lidocaine at the base of the beak led to a significant reduction of the MAP increase after Pinch [9].