PMID- 29135651
STAT- In-Data-Review
LR  - 20180829
IS  - 1944-7884 (Electronic)
IS  - 1525-4135 (Linking)
VI  - 77
IP  - 2
DP  - 2018 Feb 1
TI  - Comparison of the Pharmacokinetics and Pharmacodynamics of Single-Dose Tenofovir 
      Vaginal Film and Gel Formulation (FAME 05).
PG  - 175-182
LID - 10.1097/QAI.0000000000001587 [doi]
AB  - OBJECTIVE: Although preexposure prophylaxis with oral tenofovir (TFV) disoproxil 
      fumarate/emtricitabine reduces HIV acquisition rates, poor adherence to and
      acceptability of daily vaginal gels have led to development of vaginal film
      formulations to improve adherence and, potentially, to enable episodic use. STUDY
      DESIGN: In this 2-arm, cross-over study of a fast-dissolving tenofovir film (40
      mg) compared with a previously studied semisolid tenofovir 1% gel (40 mg), 10
      healthy women received a single vaginal dose of each study product. Clinical,
      pharmacokinetic, and antiviral assessments were performed over 1 week after dose.
      RESULTS: Nine of 10 participants experienced mild to moderate adverse effects,
      similar between products, with no severe adverse events or events attributed to
      study products. TFV concentrations after film dosing exceeded concentrations
      after gel dosing in plasma between 8 and 24 hours (P </= 0.02). TFV
      concentrations in cervicovaginal fluid and both TFV and TFV diphosphate
      concentrations in cervical tissue homogenates were higher after film dosing (all 
      P values < 0.04). The differences ranged from median (interquartile range)
      2.9-fold (1.1, 9.0; midvaginal cervicovaginal fluid) to 4.4-fold (2.9, 7.7;
      plasma). Neither film nor gel demonstrated reduced cervical tissue biopsy
      infectivity after ex vivo HIV challenge. CONCLUSION: Single-dose tenofovir film
      demonstrated consistently higher concentrations in plasma and cervicovaginal
      samples when compared with gel during the first day after dosing. Single-dose
      cervical tissue TFV-diphosphate concentrations at 5 hours exceeded steady-state
      concentrations previously reported with daily oral Truvada dosing. Tenofovir film
      may provide an alternative to tenofovir oral and gel formulations. Clinical
      efficacy remains to be tested.
FAU - Robinson, Jennifer A
AU  - Robinson JA
AD  - Medicine (Clinical Pharmacology).
FAU - Marzinke, Mark A
AU  - Marzinke MA
AD  - Medicine (Clinical Pharmacology).
AD  - Pathology, Johns Hopkins University, Baltimore, MD.
FAU - Fuchs, Edward J
AU  - Fuchs EJ
AD  - Medicine (Clinical Pharmacology).
FAU - Bakshi, Rahul P
AU  - Bakshi RP
AD  - Medicine (Clinical Pharmacology).
FAU - Spiegel, Hans M L
AU  - Spiegel HML
AD  - Kelly Government Solutions, Contractor to Division of AIDS, PMPRB/Prevention
      Sciences Program, Division of AIDS, NIAID, NIH, Rockville, MD.
FAU - Coleman, Jenell S
AU  - Coleman JS
FAU - Rohan, Lisa C
AU  - Rohan LC
AD  - Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA.
AD  - Magee-Womens Research Institute, Pittsburgh, PA.
FAU - Hendrix, Craig W
AU  - Hendrix CW
AD  - Medicine (Clinical Pharmacology).
LA  - eng
GR  - T32 GM066691/GM/NIGMS NIH HHS/United States
GR  - U19 AI082639/AI/NIAID NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Acquir Immune Defic Syndr
JT  - Journal of acquired immune deficiency syndromes (1999)
JID - 100892005
PMC - PMC5821271
MID - NIHMS917323
EDAT- 2017/11/15 06:00
MHDA- 2017/11/15 06:00
CRDT- 2017/11/15 06:00
PMCR- 2019/02/01 00:00
PHST- 2019/02/01 00:00 [pmc-release]
PHST- 2017/11/15 06:00 [pubmed]
PHST- 2017/11/15 06:00 [medline]
PHST- 2017/11/15 06:00 [entrez]
AID - 10.1097/QAI.0000000000001587 [doi]
PST - ppublish
SO  - J Acquir Immune Defic Syndr. 2018 Feb 1;77(2):175-182. doi: