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.
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.
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DOI：
10.1007/s13346-018-0538-0
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发表时间：
2018-10
影响因子：
5.4
通讯作者：
Smith JM
中科院分区：
文献类型：
--
作者：
Pereira LE;Singletary T;Martin A;Dinh CT;Deyounks F;Holder A;McNicholl J;Buckheit KW;Buckheit RW Jr;Ham A;Katz DF;Smith JM
本研究评价了不同凝胶体积对药代动力学的影响。将含有非核苷类逆转录酶抑制剂IQP-0528和替诺福韦(TFV)的凝胶IQB4012应用于尾辫猕猴的阴道和直肠。阴道凝胶体积(1%载药量)为0.5或1.5毫升；冲洗后，直肠涂抹1或4毫升凝胶。在0、2、4和24小时采集血液、阴道和直肠液，在4和24小时采集阴道和直肠组织活检。在匹配的时间点，两种药物在室内凝胶体积之间的浓度没有统计学差异。用药后，阴道组织、阴道液和直肠液中IQP-0528浓度的中位数分别为~104~105 ng/g、105~106 ng/ml和103~105 ng/ml(超过24小时)。在匹配的时间点，阴道TFV中值浓度比IQP-0528水平低1-2个对数。应用直肠凝胶后，直肠液中IQP-0528和TFV浓度的中位数分别为~103~105 ng/ml和~102~103 ng/ml。这两种药物在直肠组织中的浓度都很低(~101-103 ng/g)。对于1毫升的凝胶，一半的直肠组织样本中这两种药物的浓度都无法检测到，超过一半的直肠液样本中的TFV浓度无法检测到。这些结果表明，阴道和直肠之间的药物释放存在差异，较小的阴道凝胶体积可能不会显著影响杀菌剂PK和预防潜力。然而，直肠凝胶量对两种药物的PK的影响不是很确定。
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 ~ 104–105 ng/g, 105–106 ng/ml, and 103–105 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 ~ 103–105 ng/ml and ~ 102–103 ng/ml, respectively. Concentrations of both drugs sampled in rectal tissues were low (~ 101–103 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.
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影响因子：
3.6
作者：
Carballo-Diéguez A;Dolezal C;Bauermeister JA;O'Brien W;Ventuneac A;Mayer K
通讯作者：
Mayer K
异性肛门性交：艾滋病毒的被忽视的危险因素？
DOI：
10.1111/aji.12064
发表时间：
2013-02
期刊：
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子：
--
作者：
Baggaley RF;Dimitrov D;Owen BN;Pickles M;Butler AR;Masse B;Boily MC
通讯作者：
Boily MC
影响因子：
3.1
作者：
Carballo-Dieguez, Alex;Exner, Theresa;Mayer, Kenneth H.
通讯作者：
Mayer, Kenneth H.
影响因子：
2.5
作者：
Brody, Stuart;Weiss, Petr
通讯作者：
Weiss, Petr
影响因子：
2.9
作者：
Burns, Rebecca N.;Hendrix, Craig W.;Chaturvedula, Ayyappa
通讯作者：
Chaturvedula, Ayyappa