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Title: The clinical and Pharmacokinetic impact of altering the route of drug administration in obstetrics and gynaecology
Author: Sharma, Sunita
Awarding Body: Imperial College London (University of London)
Current Institution: Imperial College London
Date of Award: 2007
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The non-oral route of drug administration has been successfully utilised in most areas of medicine. Over time, our understanding of the mechanism of absorption from these routes has expanded and newer agents are constantly being explored. In women's health, the vaginal route is now firmly established as a route of administration for a number of medications. Though the potential of the vaginal route has been known for centuries, its use in clinical practice has been slow to establish. Prostaglandins as a group of drugs highlight this issue quite well. When prostaglandins were introduced to obstetrics and gynaecology in the 1960s, they were initially administered orally or parentally but the side effect profile by these routes limited their routine use in clinical practice. This was however overcom.e by using the vaginal route of administration and it is . now standard that prostaglandins are administered vaginally. Nevertheless, it took 10 years of prostaglandin research prior to the vaginal route being established in normal clinical practice. Since then several oth~r agents are routinely administered by this route and will be discussed during the course of this thesis. Inspired by the success of misoprostol administered through alternative non oral routes, I wanted to study the rationale of administering drugs used in obstetrics and gynaecology by non oral routes and undertook studies designee to evaluate the pharmacokinetic and/or clinical impact of non oral routes for azithromycin, mifepristone and misoprostol. Azithromycin has never been used by the vaginal route while mifepristone administered vaginally has been investigated in one small pharmacokinetic stUdy. Also the pharmacokinetics of the rectal route of misoprostol administration in early pregnancy has never been investigated. Thus the work described in this thesis has aimed to explore the non oral route of drug administration for three commonly used drugs in women's health. The studies undertaken involved 157 women and were done over a period of 30 months. These studies utilised different methodological approaches. Tissue pharmacokinetic assays was used for the assessment of pelvic absorption of azithromycin, clinical assessment was used for vaginal mifepristone and vaginal misoprostol in early medical termination of pregnancy, serum pharmacokinetic assays was used for the systemic absorption of misoprostol by the oral, vaginal and rectal route and objective assessment was used for the cervical priming by misoprostol in one hour.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available