Placental transfer of temazepam and fentanyl in early human pregnancy.
The placental transfer of temazepam and fentanyl was studied in 37 women undergoing surgical termination of pregnancy between 12 and 17 weeks. The women received temazepam 10 mg, approximately 1 h pre-operatively and fentanyl 2 &mgr;g/kg intravenously, at induction of anaesthesia. A single 2 ml fetal blood sample was taken from each anaesthetized subject using an ultrasound-guided trans-abdominal puncture at either 5, 10, 15 or 20 min after administration of fentanyl. A maternal blood sample was collected simultaneously and both were assayed for temazepam and fentanyl. Both drugs were detected in all fetal serum samples. Fetal:maternal (F:M) drug concentration ratio was 0.38 for temazepam, which did not change between 60 and 120 min after oral administration to the mother. Overall F:M ratio for fentanyl was 1.87 for fentanyl, which increased from 1.42 at 5 min to 2.6 at 20 min. F:M ratio of fentanyl concentrations increased with time (r = 0.48, P < 0.003), whereas F:M ratio of temazepam concentrations did not change significantly with time, between 50 and 120 min after the drug was administered to the mother (r = 0.32, P = 0.06). F:M ratios changed with gestational age of the fetus for both drugs, increasing as gestational age increased in the case of temazepam (r = 0.47, P = 0.003) and decreasing in the case of fentanyl (r = 0.38, P = 0.02). These changes can be explained by variation in uterine blood flow, trophoblast membrane thickness and feto-placental metabolism. These results also indicate that the in-vitro study of these drugs is unlikely to reflect the in-vivo situation in early pregnancy.
Cooper
Jacqueline
J
Department of Anaesthetics, Royal Free Hospital, University College London Medical School, London, UK.
Jauniaux
Eric
E
Gulbis
Beatrice
B
Bromley
Lesley
L