title: Pharmacokinetic studies of norethisterone-3-oxime and norethisterone-3-oxime acetate in rhesus monkey.
abstract: After [6,7-3H]-labelled norethisterone-3-oxime (NETO) and norethisterone-3-oxime acetate (NETO-AC) were given intravenously or orally through a nasal tube with 1 mg of respective unlabelled steroid to Rhesus monkey, serum samples were collected at various periods, and radioactivity was counted with or without reverse-phase HPLC separation in advance. Pharmacokinetics of NETO and NETO-AC were compared with those of norethisterone (NET) and norethisterone acetate (NET-AC) respectively which were studied in a similar experimental design. The results indicated that the serum concentration-time curve of NETO and NET could be adequately described by a two-compartment model. Average t 1/2 ka, t 1/2 alpha and t 1/2 beta with standard deviation for oral administration were 0.21 +/- 0.08 (h), 1.28 +/- 0.31 (h) and 10.01 +/- 4.59 (h) for NET and 0.37 +/- 0.81 (h), 0.90 +/- 0.26 (h) and 8.55 +/- 2.21 (h) for NETO respectively. NETO metabolized to NET which had a similar serum profile with its precursor. NET-AC also metabolized to NET, but more rapidly. It disappeared from blood 8-12 h after nasal feeding. NETO-AC was non-detectable at all when given orally because it metabolized immediately and extensively in the animal body. Its major metabolites, NETO, NET and NET-AC already appeared in the first blood sample drawn 15 min after administration. NETO-AC, when injected intravenously, declined abruptly and could not be detected 4 h later. Among the metabolites, only the deacetylated products (NET and NETO) reached relatively higher levels and sustained longer in blood.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Family Planning Research Institute, Tongji Medical University, Wuhan.
authors.forename: D Z
authors.initials: DZ
authors.lastname: Li
authors.forename: G M
authors.initials: GM
authors.lastname: Fu
authors.forename: M D
authors.initials: MD
authors.lastname: Zuo
authors.forename: M Y
authors.initials: MY
authors.lastname: Zhou
authors.forename: X L
authors.initials: XL
authors.lastname: Zhao
authors.forename: G P
authors.initials: GP
authors.lastname: Wang
authors.forename: Z N
authors.initials: ZN
authors.lastname: Wei
mesh_terms: D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D008253:Macaca mulatta; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000077563:Norethindrone Acetate; D045167:Progesterone Congeners / Q000493:pharmacokinetics*
chemical_list: D045167:Progesterone Congeners; C074736:norethisterone-3-oxime acetate; C016623:norethisterone-3-oxime; D000077563:Norethindrone Acetate; D009640:Norethindrone