Differential Bidirectional Transfer of Indinavir in the Isolated Perfused Human Placenta

Sudhakaran, Sreeja; Ghabrial, Hany; Nation, Roger L.; Kong, David Chee Ming; Gude, Neil M; Angus, Peter W; Rayner, Craig R.

doi:10.1128/aac.49.3.1023-1028.2005

Cited by 40 publications

(38 citation statements)

References 39 publications

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“…One group published two reports of indinavir models; in the earlier study the mean ± standard deviation clearance index was 0.39 ± 0.09 (n=5) [95]. This is perhaps surprising given the poor transfer in vivo as shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Protecting the Fetus Against HIV Infection: A Systematic Review of Placental Transfer of Antiretrovirals

McCormack

Best

2014

Clin Pharmacokinet

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Background Maternal-fetal transfer of antiretroviral drugs contributes to prevention of vertical transmission of HIV. Objective This systematic review discusses published studies containing data pertaining to the pharmacokinetics of placental transfer in humans, including paired cord and maternal plasma samples collected at the time of delivery as well as ex vivo placental perfusion models. Methods Articles pertaining to placental transfer of antiretrovirals were identified from PubMed, from references of included articles, and from U.S. Department of Health and Human Services Panel on Treatment of HIV-infected Pregnant Women and Prevention of Perinatal Transmission guidelines. Articles from non-human animal models or that had no original maternal-fetal transfer data were excluded. PRISMA guidelines were followed. Results A total of 103 published studies were identified. Data across studies appeared relatively consistent for the nucleoside reverse transcriptase inhibitors (NRTIs) and the non-nucleotide reverse transcriptase inhibitors (NNRTIs), with cord to maternal ratios approaching 1 for many of these agents. The protease inhibitors atazanavir and lopinavir exhibited consistent maternal-to-fetal transfer across studies, although the transfer may be influenced by variations in drug-binding proteins. The protease inhibitors indinavir, nelfinavir, and saquinavir exhibited unreliable placental transport, with cord blood concentrations that were frequently undetectable. Limited data, primarily from case reports, indicate that darunavir and raltegravir provide detectable placental transfer. Conclusion These findings appear consistent with current guidelines of using two NRTIs plus an NNRTI, atazanavir/ritonavir, or lopinavir/ritonavir to maximize placental transfer as well as to optimally suppress maternal viral load. Darunavir/ritonavir and raltegravir may reasonably serve as second-line agents.

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Section: Resultsmentioning

confidence: 99%

Protecting the Fetus Against HIV Infection: A Systematic Review of Placental Transfer of Antiretrovirals

McCormack

Best

2014

Clin Pharmacokinet

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“…In the materno-to-fetal direction, the perfusions were validated if the transfer rate of antipyrine was above the generally accepted threshold of 20% [11], whereas a threshold of antipyrine transfer rate above the mean value of 15% previously reported by Challier et al and Sudhakaran et al [17,18] was arbitrarily chosen to validate the feto-to-maternal perfusions.…”

Section: Calculation Methodsmentioning

confidence: 99%

Bidirectional placental transfer of Bisphenol A and its main metabolite, Bisphenol A-Glucuronide, in the isolated perfused human placenta

Corbel

Gayrard

Puel

et al. 2014

Reproductive Toxicology

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“…Inhibition of P-gp activity in the placenta can affect the distribution and consequently the fetal toxicity and/or efficacy of P-gp substrate drugs [91][92][93][94]. Drug-drug interactions should be considered very carefully in pregnant or lactating breast cancer patients who will be treated with anticancer drugs, substrates for P-gp, such as anthracyclines.…”

Section: Pharmacological and Toxicological Functionsmentioning

confidence: 99%

Concise Review: Clinical Relevance of Drug–Drug and Herb–Drug Interactions Mediated by the ABC Transporter ABCB1 (MDR1, P-glycoprotein)

et al. 2007

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Key Words. P-glycoprotein • Drug interaction • Complementary and alternative medicine • CAM • Pharmacokinetics Pharmacodynamics LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Identify important sources of variability in drug exposure caused by drug interactions mediated by P-glycoprotein.2. Describe how unwanted drug-drug interactions may lead to unexpected serious toxicity or undertreatment.3. Prevent these interactions by individualizing pharmacotherapy; this means selecting noninteracting drugs or adapting the dose of (the) interacting drug(s).Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTThe importance of P-glycoprotein (P-gp) in drug-drug interactions is increasingly being identified. P-gp has been reported to affect the pharmacokinetics of numerous structurally and pharmacologically diverse substrate drugs. Furthermore, genetic variability in the multidrug resistance 1 gene influences absorption and tissue distribution of drugs transported. Inhibition or induction of P-gp by coadministered drugs or food as well as herbal constituents may result in pharmacokinetic interactions leading to unexpected toxicities or undertreatment. On the other hand, modulation of P-gp expression and/or activity may be a useful strategy to improve the pharmacological profile of anticancer P-gp substrate drugs. In recent years, the use of complementary and alternative medicine (CAM), like herbs, food, and vitamins, by cancer patients has increased significantly. CAM use substantially increases the risk for interactions with anticancer drugs, especially because of the narrow therapeutic window of these compounds. However, for most CAMs, it is unknown whether they affect metabolizing enzymes and/or drug transporter activity. Clinically relevant interactions are reported between St John's wort or grapefruit juice and anticancer as well as nonanticancer drugs. CAM-drug interactions could explain, at least in part, the large interindividual variation in efficacy and toxicity associated with drug therapy in both cancer and noncancer patients.

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Differential Bidirectional Transfer of Indinavir in the Isolated Perfused Human Placenta

Cited by 40 publications

References 39 publications

Protecting the Fetus Against HIV Infection: A Systematic Review of Placental Transfer of Antiretrovirals

Protecting the Fetus Against HIV Infection: A Systematic Review of Placental Transfer of Antiretrovirals

Bidirectional placental transfer of Bisphenol A and its main metabolite, Bisphenol A-Glucuronide, in the isolated perfused human placenta

Concise Review: Clinical Relevance of Drug–Drug and Herb–Drug Interactions Mediated by the ABC Transporter ABCB1 (MDR1, P-glycoprotein)

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