TY - JOUR
T1 - Pharmacokinetics of progesterone in postmenopausal women
T2 - 1. Pharmacokinetics following intravaginal administration
AU - Mircioiu, C.
AU - Perju, A.
AU - Neagu, A.
AU - Griu, E.
AU - Calin, G.
AU - Miron, D. S.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1998
Y1 - 1998
N2 - 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 (t(max)) 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 c(max) and AUC, and an increase in t(max) following a reducing in the rate and extent of adsorption. In the case of ME suppositories, the variability in AUC, c(max) and t(max) 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.
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 (t(max)) 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 c(max) and AUC, and an increase in t(max) following a reducing in the rate and extent of adsorption. In the case of ME suppositories, the variability in AUC, c(max) and t(max) 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.
KW - Pharmacokinetics
KW - Progesterone
KW - Vaginal suppositories
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U2 - 10.1007/BF03192299
DO - 10.1007/BF03192299
M3 - Article
C2 - 9842982
AN - SCOPUS:0031796036
SN - 0378-7966
VL - 23
SP - 391
EP - 396
JO - European Journal of Drug Metabolism and Pharmacokinetics
JF - European Journal of Drug Metabolism and Pharmacokinetics
IS - 3
ER -