PMID- 9842982
OWN - NLM
STAT- MEDLINE
DCOM- 19990201
LR  - 20181113
IS  - 0378-7966 (Print)
IS  - 0378-7966 (Linking)
VI  - 23
IP  - 3
DP  - 1998 Jul-Sep
TI  - Pharmacokinetics of progesterone in postmenopausal women: 1. Pharmacokinetics 
      following intravaginal administration.
PG  - 391-6
AB  - Progesterone was administered to postmenopausal women in a form of vaginal 
      suppositories containing 100 and 200 mg active substance in Butyrum cacao (BC) 
      and Massa estarinum (ME), a base with emulsifying properties. In the case of 
      single doses, blood samples were taken at 2, 4, 6, 24, 48 and 72 h. Another group 
      of patients received vaginal suppositories (100 mg progesterone) once a day for a 
      6 day period, with blood samples taken 12 h after each administration. The plasma 
      levels of progesterone were evaluated by radioimmunoassay. The time of maximum 
      concentration (tmax) was 4 h in most cases, and 6 h in the others. The plasma 
      levels were not dose-proportional. Peak plasma concentrations were in the range 
      of 10-15 ng/ml with a mean of 10.5 ng/ml for the 100 mg and 12 ng/ml for the 200 
      mg doses. The ratio of the mean area under the curve (AUC) for 200 mg and the 
      mean AUC for the 100 mg dose was found to be 1.37. Replacing BC with ME resulted 
      in the lowering of cmax and AUC, and an increase in tmax following a reducing in 
      the rate and extent of adsorption. In the case of ME suppositories, the 
      variability in AUC, cmax and tmax was greater compared to that observed with the 
      BC suppositories. Elimination half-time was in the range of 9-10 h for BC and 14 
      h for ME suppositories. In vitro assessment of the release kinetics from a 
      hydrophobic and an emulsion type base confirmed previous findings: the latter 
      base assured better pharmaceutical availability. The repeated doses did not seem 
      to produce an accumulation of progesterone in the plasma. On the contrary, a 
      small decrease in plasma levels over time appeared during the 6 day period. 
      Numerical analysis revealed an excellent goodness of fit for the in vivo 
      experimental data via biexponential curves, i.e. a pseudomonocompartmental model.
FAU - Mircioiu, C
AU  - Mircioiu C
AD  - Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, Bucharest, 
      Romania.
FAU - Perju, A
AU  - Perju A
FAU - Neagu, A
AU  - Neagu A
FAU - Griu, E
AU  - Griu E
FAU - Calin, G
AU  - Calin G
FAU - Miron, D S
AU  - Miron DS
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PL  - France
TA  - Eur J Drug Metab Pharmacokinet
JT  - European journal of drug metabolism and pharmacokinetics
JID - 7608491
RN  - 0 (Emulsions)
RN  - 0 (Suppositories)
RN  - 4G7DS2Q64Y (Progesterone)
SB  - IM
MH  - Administration, Intravaginal
MH  - Area Under Curve
MH  - Biological Availability
MH  - Dose-Response Relationship, Drug
MH  - Emulsions
MH  - Female
MH  - Humans
MH  - Metabolic Clearance Rate
MH  - Models, Biological
MH  - *Postmenopause
MH  - Progesterone/administration & dosage/blood/*pharmacokinetics
MH  - Statistics as Topic
MH  - Suppositories/administration & dosage/pharmacokinetics
EDAT- 1998/12/08 00:00
MHDA- 1998/12/08 00:01
CRDT- 1998/12/08 00:00
PHST- 1998/12/08 00:00 [pubmed]
PHST- 1998/12/08 00:01 [medline]
PHST- 1998/12/08 00:00 [entrez]
AID - 10.1007/BF03192299 [doi]
PST - ppublish
SO  - Eur J Drug Metab Pharmacokinet. 1998 Jul-Sep;23(3):391-6. doi: 
      10.1007/BF03192299.