Targeted drug delivery in gynaecology: the first uterine pass effect

Détails

ID Serval
serval:BIB_0AB820FB5D90
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Targeted drug delivery in gynaecology: the first uterine pass effect
Périodique
Human Reproduction
Auteur(s)
Bulletti  C., de Ziegler  D., Flamigni  C., Giacomucci  E., Polli  V., Bolelli  G., Franceschetti  F.
ISSN
0268-1161
Statut éditorial
Publié
Date de publication
05/1997
Peer-reviewed
Oui
Volume
12
Numéro
5
Pages
1073-9
Notes
Comparative Study
In Vitro
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Résumé
The objective was to verify the hypothesis of a 'first uterine pass effect' or direct preferential vagina-to-uterus transport, suggested by the evidence of higher than expected uterine tissue concentrations after vaginal administration of progesterone; we used a human ex-vivo uterine perfusion model. A mixture of tritiated (3H) and unlabelled progesterone was applied to the cuff of vaginal tissue remaining attached to the cervix after hysterectomy. At the end of the perfusion period (up to 12 h), 3H and 14C radioactivity was measured in samples of uterine tissue. Tritiated water and [14C]dextran were tested to determine the extent of non-specific vagina-to-uterus transport (leaks). Finally, sections of uterine tissue exposed only to [3H]progesterone were prepared for autoradiography. By 4-5 h after application progesterone had diffused to the entire uterus and had reached a steady state; 4 h after application, progesterone concentrations reached 185 +/- 155 and 254 +/- 305 ng/100 mg of endometrial and myometrial tissue respectively. Endometrial extraction of progesterone was higher when the experiment was performed on uteri obtained during the luteal phase (280 +/- 156 ng/100 mg of endometrial tissue) than those removed during the proliferative phase of the menstrual cycle (74 +/- 28 ng/100 mg of endometrial tissue). These data demonstrate that a 'first uterine pass effect' occurs when drugs are delivered vaginally, thereby providing an explanation for the unexpectedly high uterine concentrations relative to the low serum concentration observed after vaginal administration. Hence, the vaginal route permits targeted drug delivery to the uterus, thereby maximizing the desired effects while minimizing the potential for adverse systemic effects.
Mots-clé
Administration, Intravaginal Adult Autoradiography Biological Transport Carbon Radioisotopes Dextrans/metabolism Endometrium/metabolism Female Humans Hysterectomy Menstrual Cycle/*physiology Middle Aged Myometrium/metabolism Perfusion Progesterone/*administration & dosage/*pharmacokinetics Time Factors Tritium Uterus/*metabolism Vagina/*metabolism
Pubmed
Web of science
Création de la notice
28/02/2008 12:37
Dernière modification de la notice
03/03/2018 13:34
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