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Placental and blood-CSF transfer of orally administered diazepam in the same person
Both placental and blood-lumbar CSF transfer of diazepam (5 mg orally) and its two metabolites, N-desmethyldiazepam and unconjugated oxazepam, was measured (by GLC) in 15 patients undergoing Caesarean section under spinal analgesia. Differing from our earlier studies with atropine (Virtanen et al. 1982; Kanto et al. 1981 & 1987), a reasonably fast penetration of diazepam and its two metabolites through the two biological membranes was found. Diazepam, N-desmethyldiazepam and to a lesser extent unconjugated oxazepam accumulated on the foetal side of the placenta, apparently due to a higher degree of plasma protein binding in the foetus. No accumulation was found in CSF, probably due to the lack of binding proteins in this tissue compartment. Concerning atropine, lumbar CSF with an incomplete drug penetration was found to be a "deeper" compartment than amniotic fluid, but in the present study with diazepam there was no clear difference between these two tissue compartments.
Both placental and blood-lumbar CSF transfer of diazepam (5 mg orally) and its two metabolites, N-desmethyldiazepam and unconjugated oxazepam, was measured (by GLC) in 15 patients undergoing Caesarean section under spinal analgesia. Differing from our earlier studies with atropine (Virtanen et al. 1982; Kanto et al. 1981 & 1987), a reasonably fast penetration of diazepam and its two metabolites through the two biological membranes was found. Diazepam, N-desmethyldiazepam and to a lesser extent unconjugated oxazepam accumulated on the foetal side of the placenta, apparently due to a higher degree of plasma protein binding in the foetus. No accumulation was found in CSF, probably due to the lack of binding proteins in this tissue compartment. Concerning atropine, lumbar CSF with an incomplete drug penetration was found to be a "deeper" compartment than amniotic fluid, but in the present study with diazepam there was no clear difference between these two tissue compartments.