title: Placental transfer of temazepam and fentanyl in early human pregnancy.
abstract: 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.
authors.affiliation: Department of Anaesthetics, Royal Free Hospital, University College London Medical School, London, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cooper
authors.forename: Eric
authors.initials: E
authors.lastname: Jauniaux
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gulbis
authors.forename: Lesley
authors.initials: L
authors.lastname: Bromley