Effect of plasma proteins on buprenorphine transfer across dually perfused placental lobule

Nanovskaya, Tatiana; Bowen, Robin S.; Patrikeeva, Svetlana; Hankins, Gary D.V.; Ahmed, Mahmoud S.

doi:10.1080/14767050802610328

Cited by 9 publications

(7 citation statements)

References 18 publications

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“…A limitation of this model is that it cannot fully incorporate nonplacental pharmacokinetic factors such as protein binding, elimination, and distribution in the maternal and fetal compartments. While protein can be added to the perfusion medium, 7 , 8 , 9 , 10 it is difficult to mimic physiological conditions since there are numerous proteins and endogenous factors that could influence binding in vivo .…”

Section: Advantages and Disadvantages Of Different Methods Used To Dementioning

confidence: 99%

The Human Placental Perfusion Model: A Systematic Review and Development of a Model to Predict In Vivo Transfer of Therapeutic Drugs

Hutson

Garcia‐Bournissen

Davis

et al. 2011

Clin Pharmacol Ther

169

118

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Dual perfusion of a single placental lobule is the only experimental model to study human placental transfer of substances in organized placental tissue. To date, there has not been any attempt at a systematic evaluation of this model. The aim of this study was to systematically evaluate the perfusion model in predicting placental drug transfer and to develop a pharmacokinetic model to account for nonplacental pharmacokinetic parameters in the perfusion results. In general, the fetal-to-maternal drug concentration ratios matched well between placental perfusion experiments and in vivo samples taken at the time of delivery of the infant. After modeling for differences in maternal and fetal/neonatal protein binding and blood pH, the perfusion results were able to accurately predict in vivo transfer at steady state (R² = 0.85, P < 0.0001). Placental perfusion experiments can be used to predict placental drug transfer when adjusting for extra parameters and can be useful for assessing drug therapy risks and benefits in pregnancy.

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Section: Advantages and Disadvantages Of Different Methods Used To Dementioning

confidence: 99%

The Human Placental Perfusion Model: A Systematic Review and Development of a Model to Predict In Vivo Transfer of Therapeutic Drugs

Hutson

Garcia‐Bournissen

Davis

et al. 2011

Clin Pharmacol Ther

169

118

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“…The presence and shared physiological roles of serum albumin in all vertebrates makes the understanding of this interaction helpful in determining the fates of these potential toxicants and their distribution to sensitive tissues in humans and other animals. This includes the HSA-mediated transfer of drugs and other xenobiotics transplacentally to the developing fetus, − which may implicate OH-PCBs and PCB sulfates in the neurodevelopmental effects associated with PCB exposure. This potential for retention and redistribution of PCB sulfates supports the idea that this has been a largely overlooked component of the overall picture of PCB exposure and toxicity.…”

Section: Resultsmentioning

confidence: 99%

Sulfation of Lower Chlorinated Polychlorinated Biphenyls Increases Their Affinity for the Major Drug-Binding Sites of Human Serum Albumin

Rodríguez

Lehmler

et al. 2016

Environ. Sci. Technol.

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The disposition of toxicants is often affected by their binding to serum proteins, of which the most abundant in humans is serum albumin (HSA). There is increasing interest in the toxicities of environmentally persistent polychlorinated biphenyls (PCBs) with lower numbers of chlorine atoms (LC-PCBs) due to their presence in both indoor and outdoor air. PCB sulfates derived from metabolic hydroxylation and sulfation of LC-PCBs have been implicated in endocrine disruption due to high affinity-binding to the thyroxine-carrying protein, transthyretin. Interactions of these sulfated metabolites of LC-PCBs with HSA, however, have not been previously explored. We have now determined the relative HSA-binding affinities for a group of LC-PCBs and their hydroxylated and sulfated derivatives by selective displacement of the fluorescent probes 5-dimethylamino-1-naphthalenesulfonamide and dansyl--proline from the two major drug-binding sites on HSA (previously designated as Site I and Site II). Values for half-maximal displacement of the probes indicated that the relative binding affinities were generally PCB sulfate ≥ OH-PCB > PCB, although this affinity was site- and congener-selective. Moreover, specificity for Site II increased as the numbers of chlorine atoms increased. Thus, hydroxylation and sulfation of LC-PCBs result in selective interactions with HSA which may affect their overall retention and toxicity.

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“…The protein binding data for opioids seem to explain the results of the present study. More than 90% of BPN is bound to plasma albumin, gamma-globulin and alpha-acid glycoprotein 69 – 71 . Thus, the small free fraction available for lipid sequestration may be responsible for the relatively low value of disposition coefficient obtained in the ultracentrifugation test.…”

Section: Discussionmentioning

confidence: 99%

Predicting the efficacy of opioid sequestration by intravenous lipid emulsion using biologically relevant in vitro models of drug distribution

Tikhomirov

Jajor

Śniegocki

et al. 2022

Sci Rep

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Intravenous lipid emulsions (ILE), among other uses, are utilized in the treatment of poisonings caused by lipophilic substances. The body of evidence regarding the benefits of this treatment is growing but information about opioids-ILE interaction is still very scarce. In this work, the impact of ILE on the distribution of buprenorphine, fentanyl and butorphanol used in various concentrations (100–500 ng/ml) was investigated. Two different in vitro models were used: disposition of the drugs in plasma after ultracentrifugation and distribution into the simulated biophase (cell monolayer of 3T3 fibroblasts or J774.E macrophages). We confirmed the ability of ILE to sequester the three drugs of interest which results in their decrease in the aqueous part of the plasma by 34.2–38.2%, 11.7–28.5% and 6.0–15.5% for buprenorphine, fentanyl and butorphanol, respectively. Moreover, ILE affected the drug distribution to the biophase in vitro, however, in this case the drug concentration in cells decreased by 97.3 ± 3.1%, 28.6 ± 5.4% and 13.0 ± 7.5% for buprenorphine, fentanyl and butorphanol, respectively. The two models revealed notable differences in ILE’s potential for drug sequestration, especially for buprenorphine. Similar, but not as pronounced tendencies were observed for the two other drugs. These discrepancies may result from the difference in protein abundance and resulting drug-protein binding in both systems. Nevertheless, the results obtained with both in vitro models correlated well with the partition coefficient (logP) values for these drugs.

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Effect of plasma proteins on buprenorphine transfer across dually perfused placental lobule

Cited by 9 publications

References 18 publications

The Human Placental Perfusion Model: A Systematic Review and Development of a Model to Predict In Vivo Transfer of Therapeutic Drugs

The Human Placental Perfusion Model: A Systematic Review and Development of a Model to Predict In Vivo Transfer of Therapeutic Drugs

Sulfation of Lower Chlorinated Polychlorinated Biphenyls Increases Their Affinity for the Major Drug-Binding Sites of Human Serum Albumin

Predicting the efficacy of opioid sequestration by intravenous lipid emulsion using biologically relevant in vitro models of drug distribution

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