The uptake of transdermal fentanyl in a pregnant sheep model

Objective: To evaluate the maternal and foetal uptake of transdermal fentanyl patch applied to the groin of pregnant sheep following surgery. Study design; Prospective series. Animals: A group of 16 singleton pregnant sheep underwent anaesthesia for laparotomy, hysterotomy and instrumentation of the foetus. Of these ewes 10 (101 ± 12 days of gestation) were used to evaluate the maternal uptake of transdermal fentanyl, and the efficacy of the drug in the postoperative period (n = 10). To determine the extent of transplacental transfer of fentanyl, six ewes from the group of 10, and six other ewes (92 ± 1 days’ gestation) were studied. Methods: A 75 μg hour⁻¹ fentanyl patch was placed onto the woolless skin of the medial thigh close to the groin at the end of surgery. Maternal blood samples were collected from the cephalic or jugular vein, and pain and sedation scores were determined, prior to application of the patch (time 0) and at 3, 6, 12, 24, 36 and 48 hours after. A commercial Fentanyl ELISA kit was used to determine the concentration of fentanyl. Paired maternal and foetal blood samples were collected 48 hours after surgery. Animals were euthanized at the end of the study. Data were tested for normality and compared with Student t test or one-way ANOVA and are expressed as mean ± standard deviation or median (range). Results: Recovery from anaesthesia and surgery was uneventful in all ewes. The dose of fentanyl was 1.4 ± 0.2 μg kg⁻¹ hour⁻¹. The maximum maternal plasma concentration of fentanyl was 0.547 ng mL⁻¹ (range, 0.349–0.738 ng mL⁻¹) at 12 hours. After 48 hours, the concentration of fentanyl was 0.381 ng mL⁻¹ (range, 0.211–0.487 ng mL⁻¹; maternal) and 0.295 ng mL⁻¹ (range, 0.185–0.377 ng mL⁻¹; foetal; p = 0.175). The placental transfer rate of fentanyl was 77%. Conclusions and clinical relevance: The uptake of fentanyl varied between animals. The placental transfer rate of fentanyl was 77%.