Effects of gel volume on pharmacokinetics for vaginal and rectal applications of combination DuoGel-IQB4012, a dual chamber-dual drug HIV microbicide gel, in pigtailed macaques
| Autor: | Tyana Singletary, Karen W. Buckheit, Chuong Dinh, Lara E. Pereira, Amy Martin, Angela Holder, Anthony S. Ham, Robert W. Buckheit, Janet M. McNicholl, David F. Katz, Frank Deyounks, James M. Smith |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Drug medicine.medical_specialty Anti-HIV Agents media_common.quotation_subject 030106 microbiology Urology Pharmaceutical Science Rectum Pyrimidinones Article 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Administration Rectal Microbicide Rectal Gel medicine Animals 030212 general & internal medicine Tenofovir media_common Reverse-transcriptase inhibitor business.industry medicine.anatomical_structure Drug delivery Vaginal Creams Foams and Jellies Vagina Macaca Female business medicine.drug |
| Zdroj: | Drug Delivery and Translational Research. 8:1180-1190 |
| ISSN: | 2190-3948 2190-393X |
| Popis: | This study evaluated effects of differing gel volumes on pharmacokinetics (PK). IQB4012, a gel containing the non-nucleoside reverse transcriptase inhibitor IQP-0528 and tenofovir (TFV), was applied to the pigtailed macaque vagina and rectum. Vaginal gel volumes (1% loading of both drugs) were 0.5 or 1.5 ml; following wash-out, 1 or 4 ml of gel were then applied rectally. Blood, vaginal, and rectal fluids were collected at 0, 2, 4, and 24 h. Vaginal and rectal tissue biopsies were collected at 4 and 24 h. There were no statistically significant differences in concentrations for either drug between gel volumes within compartments at matched time points. After vaginal gel application, median IQP-0528 concentrations were ~ 10(4)–10(5) ng/g, 10(5)–10(6) ng/ml, and 10(3)–10(5) ng/ml in vaginal tissues, vaginal fluids, and rectal fluids, respectively (over 24 h). Median vaginal TFV concentrations were 1–2 logs lower than IQP-0528 levels at matched time points. After rectal gel application, median IQP-0528 and TFV concentrations in rectal fluids were ~ 10(3)–10(5) ng/ml and ~ 10(2)–10(3) ng/ml, respectively. Concentrations of both drugs sampled in rectal tissues were low (~ 10(1)–10(3) ng/g). For 1 ml gel, half of sampled rectal tissues had undetectable concentrations of either drug, and over half of sampled rectal fluids had undetectable TFV concentrations. These results indicate differences in drug delivery between the vaginal and rectal compartments, and that smaller vaginal gel volumes may not significantly compromise microbicide PK and prophylactic potential. However, effects of rectal gel volume on PK for both drugs were less definitive. |
| Databáze: | OpenAIRE |
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