Microbicides 2004 Microbicides 200428-31 March 2004, Hilton London MetropoleThe conference42 million men, women and children worldwide were living with HIV by the end of December 2002 (source: UNAIDS), including five million newly-infected during that year alone. Another 45 million people will become infected between 2002 and 2010, unless the current transmission rates can be vastly reduced. Of the 42 million, 29.4 million live in sub-Saharan Africa and 58% of them are women. Not only are women more susceptible to HIV infection, many are powerless to insist on the use of condoms or other methods of protecting themselves. In this context, and with the knowledge that an effective HIV vaccine is unlikely to be available for several years, the need for an effective topical microbicide grows ever more urgent. 2004 should prove to be a landmark year in the field of microbicide development as the first Phase III trials of novel products are due to start – the next step along the road to making a microbicide available to the millions worldwide in desperate need of protection.The aims of the Microbicides 2004 conference are to:Report novel or innovative work in the microbicides fieldProvide updates on recent microbicides research, divided into three tracks: basic science, clinical science, and behavioural science (including public health and the microbicide marketplace)Provide a forum for the discussion of new developments in microbicide research including ethical, clinical, behavioural and methodological issuesPresent opportunities for knowledge-sharing between microbicide researchers, public-health workers and advocacy organisations.There will be an opening ceremony on the evening of Sunday 28 March at which politicians, policy makers and the international media are expected. The conference will run for a full three days, each of which will contain:Scientific overviews and presentations with plenary sessions, invited lecturers and presentations of original researchWorkshops to review issues unique to microbicides such as trial design and outcome measures, and ethical issues in the clinical trials of microbicidesPoster sessions. Focus on LondonFollowing the successful Microbicides conferences in Washington in 2000 and Antwerp in 2002, March 2004 sees the focus move to London.The venue is the Hilton Metropole Hotel, two minutes by taxi from Paddington station and the Heathrow Express, with a journey time from the airport of 15 minutes. The hotel is in walking distance of Hyde Park and London’s main shopping streets, and close to Imperial College. Accommodation will be available at the venue and other hotels in the vicinity.London in March offers a variety of diversions for out-of-conference relaxation, including sight-seeing and shopping; the arts and the theatre; and pubs, clubs and restaurants to suit every taste. Conference staff will be on hand to help delegates plan their spare time.To book your place or find out more information, e-mail info@microbicides2004.org.uk or telephone the Event Office on +44 (0) 20 7720 4411
Oral: invited speaker Oral: Track A Oral: Track B Oral: Track C Poster: Track A Poster: Track B Poster: Track C Abstract only Authors

02439 COMPARISON OF DRUG ABSORPTION FOLLOWING INTRAVAGINAL ADMINISTRATION TO RATS AND RABBITS

Litterst, Charles*
Shinn, W^., Ho, M^., Levalley, S.^, Mirsalis, J.^, Green, C.^
*Div. of AIDS, Niaid, Nih, Bethesda, Md, USA; ^SRI International, Menlo Park, CA, USA

Objective of the study was to compare rabbit and rat as models for evaluation of vaginal uptake and tissue distribution of drugs following intravaginal administration. Radioactive lamivudine (well absorbed orally) and ganciclovir (poorly absorbed orally) were formulated in Replense, administered in 0.5 ml, and animals placed in metabolism cages (n=3/group). Fluids/feces were collected for 48 hrs and tissue content of radioactivity was compared at 4 hrs. Rat tissues were also analyzed at 12 and 48 hrs. Less than 1% of the administered dose of either drug was found in the blood of either species at any time point, although high concentrations found in urine suggests that there was significant systemic uptake. Rats excreted 32% of lamivudine dose in 4 hr, and rabbits excreted 5%. By 48 hr, total amount of radioactivity in urine of rats and rabbits was 45% and 37%, respectively. Percent of dose in feces at 48 hr was 37% for rats and 13% for rabbits. After administration of ganciclovir to rats, 15% of the dose was found in urine and 51% in feces at 48 hr. In rabbits, 9% and 8% were recovered in 48 hr urine and feces, respectively. Less than 5% of total radioactivity from either drug remained in tissues at the end of the study. Rat tissues with the largest fraction of dose were vagina, GI tract, and large organs (muscle and skin). A similar quantity of radioactivity was recovered in most tissues for both drugs. A notable exception was rat vagina, which at 4 hr contained 8-10% of the dose for both drugs, in contrast to rabbit vagina, which contained only 0.1% of the administered dose. No drug was found in rat bladder, although from 13%-19% of total radioactivity was found in rabbit bladder. These high levels may be due to urethral transit of drug from the vagina into the bladder of rabbits. In summary, significant systemic absorption of both drugs occurs following intravaginal administration. Thus, possible systemic effects may be a concern following intravaginal administration of drugs.

Dr. Charles Litterst, Div. of AIDS, NIAID, NIH
6700B Rockledge Dr., Room 5151, Bethesda, Maryland, 20892, USA
(Telephone) 301-402-0132 (Fax) 301-435-9282 (E-mail) CLITTERST@NIAID.NIH.GOV