title: Uptake of estradiol or progesterone into the CSF following intranasal and intravenous delivery in rats.
abstract: The uptake of estradiol and progesterone into the cerebrospinal fluid (CSF) after intranasal and intravenous administration in rats was investigated. Each animal received estradiol intranasally (40 microg/rat) and by intravenous infusion (10 microg/rat) into the jugular vein using a vascular access port. Hereafter, the same set of rats was treated with progesterone intranasally (200 microg/rat) and by intravenous infusion (104 microg/rat). Following nasal delivery, both steroid hormones reach Cmax values in plasma and CSF at 15 min after administration. Intravenous infusion of estradiol and progesterone shows comparable plasma and CSF concentration-time profiles compared to the nasal route. For both hormones the AUCCSF/AUCplasma ratios (mean +/- SD) after intranasal delivery (estradiol 2.3 +/- 1.1%; progesterone 1.9 +/- 0.7%) do not differ significantly from the ratios shown after intravenous infusion (estradiol 2.0 +/- 0.6%; progesterone 2.2 +/- 0.8%). These results indicate that after nasal delivery estradiol and progesterone are rapidly absorbed into the systemic circulation, from where the non-protein bound hormones probably enter the CSF by crossing the blood-brain barrier. No extra direct nose-CSF transport could be demonstrated.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Mascha P
authors.initials: MP
authors.lastname: van den Berg
authors.forename: J Coos
authors.initials: JC
authors.lastname: Verhoef
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Romeijn
authors.forename: Frans W H M
authors.initials: FW
authors.lastname: Merkus
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D004958:Estradiol / Q000008:administration & dosage* / Q000134:cerebrospinal fluid*; D007262:Infusions, Intravenous; D008297:Male; D011374:Progesterone / Q000008:administration & dosage* / Q000134:cerebrospinal fluid*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D011374:Progesterone; D004958:Estradiol