Abstract：
:Effective antiretroviral (ARV)-based HIV prevention strategies require optimizing drug exposure in mucosal tissues; yet factors influencing mucosal tissue disposition remain unknown. We hypothesized drug transporter expression in vaginal, cervical, and colorectal tissues is a contributing factor and selected 3 efflux (ABCB1/MDR1, ABCC2/MRP2, ABCC4/MRP4) and 3 uptake (SLC22A6/OAT1, SLC22A8/OAT3, SLCO1B1/OATP1B1) transporters to further investigate based on their affinity for 2 ARVs central to prevention (tenofovir, maraviroc). Tissue was collected from 98 donors. mRNA and protein expression were quantified using qPCR and immunohistochemistry (IHC). Hundred percent of tissues expressed efflux transporter mRNA. IHC localized them to the epithelium and/or submucosa. Multivariable analysis adjusted for age, smoking, and co-medications revealed significant (P < 0.05) differences in efflux transporter mRNA between tissue types (vaginal ABCB1 3.9-fold > colorectal; vaginal ABCC2 2.9-fold > colorectal; colorectal ABCC4 2.0-fold > cervical). In contrast, uptake transporter mRNA was expressed in <25% of tissues. OAT1 protein was detected in 0% of female genital tissues and in 100% of colorectal tissues, but only in rare epithelial cells. These data support clinical findings of higher maraviroc and tenofovir concentrations in rectal tissue compared to vaginal or cervical tissue after oral dosing. Quantifying mucosal transporter expression and localization can facilitate ARV selection to target these tissues.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Nicol MR,Fedoriw Y,Mathews M,Prince HM,Patterson KB,Geller E,Mollan K,Mathews S,Kroetz DL,Kashuba ADdoi
10.1002/jcph.248subject
Has Abstractpub_date
2014-05-01 00:00:00pages
574-83issue
5eissn
0091-2700issn
1552-4604journal_volume
54pub_type
杂志文章abstract：:Direct comparisons of the pharmacokinetic (PK) and systemic pharmacodynamic (PD) properties of inhaled corticosteroids after single and multiple dosing in the same subjects are scarce. The objective of this study was to compare thePK/PDproperties of clinically equivalent, single, and multiple doses of dry-powder formu...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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abstract：:Dual inhibition of neutral endopeptidase 24.11 (NEP) and angiotensin-converting enzyme (ACE) has gained increasing interest in the treatment of hypertension, heart failure, and renoprotection. Specifically, M100240, the thioester of the dual ACE/NEP inhibitor MDL100,173, has been evaluated in the management of hyperte...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
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abstract：:Sitagliptin is an orally active, highly selective dipeptidyl peptidase IV (DPP-4) inhibitor for treatment of type 2 diabetes mellitus. This randomized, open-label, 2-part, 2-period crossover study assessed pharmacokinetics/pharmacodynamics of warfarin in the presence/absence of multiple-dose sitagliptin. Twelve partic...
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abstract：:Antibacterial drugs are among the most common medications used by pregnant women. While medical literature generally defines nitrofurantoin as an antibiotic that is safe for use during the first trimester of pregnancy, new concerns about a possible association between congenital malformations following exposure to nit...
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1981.tb05685.x
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pub_type： 杂志文章
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1994.tb04726.x
更新日期：1994-12-01 00:00:00
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pub_type： 杂志文章
doi：10.1002/j.1552-4604.1980.tb01685.x
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pub_type： 临床试验,杂志文章,多中心研究
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
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更新日期：1989-06-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
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更新日期：2009-01-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270010363476
更新日期：2011-01-01 00:00:00
abstract：:The pharmacokinetics and pharmacodynamics of intravenous famotidine were evaluated in 10 infants ranging from 5 to 19 days of age who had a therapeutic indication for the prophylactic treatment of stress ulceration. After a 0.5-mg/kg infusion of famotidine, timed serum (n = 6), urine (24-hour collection), and repeated...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1998-12-01 00:00:00
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1993.tb05611.x
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1987.tb03083.x
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pub_type： 临床试验,杂志文章
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：2000-12-01 00:00:00
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journal_title：Journal of clinical pharmacology
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更新日期：2013-05-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1984.tb02760.x
更新日期：1984-11-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1981.tb01746.x
更新日期：1981-10-01 00:00:00
abstract：:Monitoring drug levels in patients is standard practice in presentday critical care medicine. Clinical laboratories, however, are often unable to assay drug levels immediately following phlebotomy. This may result in blood samples being kept under a variety of storage conditions for nonuniform periods of time. The cur...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1988.tb03212.x
更新日期：1988-08-01 00:00:00
abstract：:The most thorough and clinically relevant approach to hypnotic drug evaluation is one that balances the strengths and weaknesses of clinical trials and sleep laboratory evaluations. Advantages of clinical trials include the ability to evaluate large numbers of subjects and specific target groups and to thoroughly asse...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,评审
doi：10.1002/j.1552-4604.1979.tb02489.x
更新日期：1979-07-01 00:00:00
