Physicochemical and Structural Properties Regulating Placental Drug Transfer
Elsevier eBooksPublished 18 July 2016
Karel Allegaert, John N. van den Anker
Citations7
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Abstract
edition: 5th
Keywords
Medicine
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European Journal of PharmacologyHuman placental transport of vinblastine, vincristine, digoxin and progesterone: contribution of P-glycoprotein
143 Citations2000Fumihiko Ushigome, Hitomi Takanaga +9 more
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Fundamental and Applied ToxicologyEvaluation of valproic acid (VPA) developmental toxicity and pharmacokinetics in Sprague-Dawley rats
140 Citations1988Pamela E. Binkerd
Oral administration of 200-800 mg/kg VPA (5-20x human therapeutic dose) from Gestational Days (GD) 8 to 17 resulted in increasing maternal toxicity at the higher doses with 100% maternal lethality at 800mg/kg.
Pharmacology & TherapeuticsDrug disposition and pharmacokinetics in the maternal-placental-fetal unit
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NatureWeak acids may act as teratogens by accumulating in the basic milieu of the early mammalian embryo
134 Citations1986Heinz Nau, William J. Scott
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American Journal of Obstetrics and GynecologyPharmacokinetics of acyclovir in the term human pregnancy and neonate
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Proceedings of the National Academy of SciencesRetinol-binding protein and transthyretin mRNA levels in visceral yolk sac and liver during fetal development in the rat.
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94 Citations1978Diane R. Biehl, Sol M. Shnider +2 more
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Out of these physical and pharmacologic characteristics, the very extensive plasma protein binding and short elimination half-life of glyburide appear to be major determinants of its minimal transplacental transfer.
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75 Citations1994Mark S. Yerby
Women with epilepsy who are of childbearing age and babies born to women with epilepsy face a higher risk of miscarriage, stillbirth, prematurity, developmental delay, and major malformations.
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74 Citations1981Heinz Nau, Rolf Baß
Following the administration of the highly toxic agent 2,3,7,8-tetrachlorodibenzo-p-dioxin to pregnant mice, exceedingly low concentrations of this substance were found in the embryo and fetus between gestational days 11 and 18.
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71 Citations1998A. Sánchez–Alcaraz, Miguel Quintana +1 more
Propofol plasma levels in the newborn at the time of delivery depend on the level in maternal plasma, and therefore on the dose used for induction and the time lapsed between the administration of the drug and the delivery of the foetus.
BJOG An International Journal of Obstetrics & GynaecologyTRANSFER OF GLUTAMIC ACID ACROSS THE HUMAN PLACENTA PERFUSED <i>IN VITRO</i>
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It is postulated that maternal glutamine, which is efficiently transferred across the placenta, contributes its amid‐N2 to the fetal synthesis of purines and pyrimidines and that the resulting surplus of glutamic acid is returned to the Placenta which removes it from the circulation and metabolizes it.
PubMedTransfer of lead via placenta and breast milk in human.
68 Citations2000P J Li, Y Z Sheng +3 more
The results suggested that transfer of lead via placenta prenatally and breast milk postnatally were possible and might pose a potential health hazard to the fetuses and the neonates.
Developmental Pharmacology and TherapeuticsClinical Pharmacokinetics in Pregnancy and Perinatology
68 Citations2017Heinz Nau
Local anaesthetic agents, both of the amide type and the ester type, are widely used to relieve pain in obstetric and gynaecological practice and the pharmacokinetics of these compounds are discussed in this review, with particular emphasis on the fetal exposure and its relationship to adverse effects on the fetus.
PubMedAcidosis, local anesthetics, and the newborn.
68 Citations1976Brown Wu, Bell Gc +1 more
Four newborn infants, born with a pH of 7.23 or below in the umbilical vein blood, showed an elevated fetal-to-maternal concentration ratio, a possible manifestation of ion trapping of a weak base following maternal epidural block with lidocaine or mepivacaine.
American Journal of Physiology-Cell PhysiologyTransfer of hydrophilic molecules by placenta and yolk sac of the guinea pig
66 Citations1977Kent L. Thornburg, J. Job Faber
Prenatal transfer of hydrophilic materials was studied in chronic guinea pig preparations and there was evidence of a nonspecific suppression of yolk sac function by surgery but no evidence of fetal catabolism of gamma globulin.
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PubMedMaternal-fetal transfer of metallic mercury via the placenta and milk.
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60 Citations2012Walter K. Kraft, John N. van den Anker
Emerging trends in the treatment of infants with NAS include the use of sublingual buprenorphine, transition to outpatient therapy, and pharmacogenetic risk stratification.
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The administration of NAC to mothers with CA achieves predictable NAC plasma concentrations in the fetus, indicating that antenatal neuroprotection may be possible for these newborns at high risk for neuroinflammation.
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There are a number of studies to suggest that the pharmacokinetics of β-lactam antibiotics are altered during pregnancy, indicating faster elimination of these antibiotics and lowered plasma concentrations.
Antimicrobial Agents and ChemotherapyPharmacokinetics and transplacental passage of imipenem during pregnancy
57 Citations1992Anna‐Riitta Heikkilä, O V Renkonen +1 more
The results indicate that an adjustment of doses of imipenem may be required when treating pregnant women because of considerable changes in imipanem pharmacokinetics during pregnancy.
American Journal of Physiology-Cell PhysiologyTaurine transport by microvillous membrane vesicles and the perfused cotyledon of the human placenta
57 Citations1990Peter I. Karl, Stanley E. Fisher
This study demonstrates that taurine uptake by the microvillous membrane of the human placenta is highly specific, of high affinity, and Na+ coupled.
Proceedings of the National Academy of SciencesTransplacental passage of insulin complexed to antibody.
55 Citations1981William Bauman, Rosalyn S. Yalow
The demonstration that antigen restricted from transplacental passage can be transferred while complexed to antibody raises the question whether such fetal exposure would induce partial or total immunologic unresponsiveness subsequently if the fetus were rechallenged with the same antigen.
Clinical Pharmacology & TherapeuticsSerum protein binding of drugs and bilirubin in newborn infants and their mothers
55 Citations1980C Hamar, Gerhard Levy
The serum protein binding of dexamethasone, diazepam, phenytoin, sulfisoxazole, and bilirubin was determined in full‐term newborn infants and their mothers immediately after delivery and positive correlations between the free fraction values of the various compounds and those of salicylic acid were found.
International ImmunopharmacologyMaternal bacterial infections impact expression of drug transporters in human placenta
54 Citations2015Vanja Petrović, Dea Kojovic +2 more
Data show that maternal infections impact the expression of key drug transporters in placenta, suggesting that materno-fetal drug transport may be altered by changes in placental expression of ABC and OATP transporter.
The Annual Review of Pharmacology and ToxicologyDeterminants of Drug Disposition and Effect in the Fetus
54 Citations1979T P Green, Robert F. OʼDea +1 more
This review considers aspects of developmental pharmacology that have not been extensively considered in previous publications, examining in particular the following subject areas: biological maturation on placental transfer, the effects of drugs on placements, fetal drug disposition, and the reac tivity of the fetus to pharmacologic agents.
European Journal of Clinical PharmacologyThe placental transfer of betamethasone
54 Citations1980M. C. Petersen, Roger L. Nation +2 more
The plasma concentrations of beta-methasone in a maternal peripheral vein (mv) and in the umbilical vein (uv) were measured at delivery in eleven patients after the administration ofBeta-mETHasone phosphate equivalent to 8 mg betamethas one.
PubMedValproic acid clearance in children with epilepsy.
52 Citations1998A. Sánchez–Alcaraz, M. B. Quintana +2 more
The relationship between clearance and age should be useful when establishing a pharmacokinetic programme for VPA monotherapy in children, and can be used to establish the initial maintenance paediatric dose of VPA in monotherapy.
Biology of ReproductionBisphenol A Disposition in the Sheep Maternal-Placental-Fetal Unit: Mechanisms Determining Fetal Internal Exposure1
50 Citations2013Tanguy Corbel, Véronique Gayrard +5 more
A physiological model was developed in ewes to determine whether the pregnancy-associated physiological changes and the metabolic specificities of the fetal-placental unit can influence BPA toxicokinetics (TK) and fetal exposure to BPA.
Expert Opinion on Drug Metabolism & ToxicologyRegulation of drug transporter expression and function in the placenta
50 Citations2015František Štaud, Martina Čečková
There is clearly a need for further preclinical and clinical studies on placental drug transporters, but such investigations must be carefully designed and the resulting data should be evaluated with great caution.
American Journal of Obstetrics and GynecologyCefazolin pharmacokinetics in maternal plasma and amniotic fluid during pregnancy
50 Citations2008Karel Allegaert, Tim Van Mieghem +6 more
Cefazolin clearance and distribution volume are increased during pregnancy, and dosing regimes to attain higher amniotic fluid concentrations were formulated.
Archives of ToxicologyThe high sensitivity of the rabbit to the teratogenic effects of 13-cis-retinoic acid (isotretinoin) is a consequence of prolonged exposure of the embryo to 13-cis-retinoic acid and 13-cis-4-oxo-retinoic acid, and not of isomerization to all-trans-retinoic acid
49 Citations1994Georg Tzimas, Heinrich Bürgin +3 more
The results suggest that the high sensitivity of the rabbit to the teratogenic effects of 13-cis-RA can be attributed mainly to the 13- cis-isomers and not to isomerization to all-trans-RA, and supports the view that embryonic AUC values should be considered as the most suitable pharmacokinetic correlate to retinoid induced teratogenesis.
British Journal of Clinical PharmacologyVigabatrin:placental transfer ‘ooin vivo‘ox and excretion into breast milk of the enantiomers
49 Citations1998A. Tran, T. O’Mahoney +4 more
The results would suggest a slow placental transfer of the vigabatrin enantiomers and that the quantity ingested through milk is small.
Archives of ToxicologyThe enantiomers of the teratogenic thalidomide analogue EM 12
49 Citations1988Hans‐Josef Schmahl, Heinz Nau +1 more
The results indicate that both enantiomers racemise with appreciable rates; this may be expected to complicate the interpretation of studies designed to evaluate stereoselective differences with respect to teratological activities of EM 12 and related substances such as thalidomide.
BJOG An International Journal of Obstetrics & GynaecologyCONCENTRATIONS OF FREE FATTY ACIDS IN MATERNAL AND UMBILICAL CORD BLOOD DURING ELECTIVE CAESAREAN SECTION
48 Citations1976M.C. Elphick, D. Hull +1 more
There was a direct and significant correlation between the umbilical v–a difference and maternal venous concentrations.
Drug SafetyP-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies: A Case-Reference Study
46 Citations2015Nur Aizati Athirah Daud, Jorieke E. H. Bergman +8 more
For several drug classes associated with specific anomalies, P-gp-mediated drug interactions are associated with an increased risk for those specific anomalies.
International Journal of Hygiene and Environmental HealthRatio of cord to maternal serum PCB concentrations in relation to their congener-specific physicochemical properties
46 Citations2014Kinga Lancz, Ľubica Murínová +9 more
The possible role of cholesterol as a transplacental transporter of PCBs is discussed and an inverse association between logKOW and lipid adjusted logC/M is found.
PubMedAntibiotic concentration in maternal blood, cord blood, and placental membranes in chorioamnionitis.
46 Citations1988Larry C. Gilstrap, Roger E. Bawdon +1 more
Based on these findings, the commonly used combination of ampicillin and gentamicin seems appropriate, although additional anaerobic coverage may be needed.
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45 Citations1994Renate Huch, A. Huch
The human placenta forms a manifest barrier to endogenous and recombinant erythropoietin, thus fulfilling the cardinal precondition for the use of recombinant ______ in the treatment of maternal pregnancy anemia.
Teratogenicity of Valproic Acid and Related Substances in the Mouse: Drug Accumulation and pHi in the Embryo During Organogenesis and Structure-Activity Considerations
44 Citations1987Heinz Nau, William J. Scott
The antiepileptic drug valproic acid is a putative human teratogen as suggested by retrospective studies, but the use of thus drug for seizure control during pregnancy was shown to result in an increased incidence of neural tube defects, in particular spina bifida aperta.
Obstetrics and GynecologyTransfer of Erythropoietin Across the Placenta Perfused In Vitro
43 Citations1997Klaus Reisenberger
There is no transport of erythropoietin across fetal membranes in a placental perfusion model ex vivo, and this finding is particularly remarkable in view of results published recently indicating the placenta as a site of eriespheric production.
Clinical and Experimental Pharmacology and PhysiologyOlanzapine Transfer By Human Placenta
43 Citations1999S. Schenker, Yuxiao Yang +3 more
The present study assessed the human transplacental transport of olanzapine, a new antipsychotic drug effective in the treatment of schizophrenia, and found it to be feasible and effective in patients with schizophrenia.
Toxicological SciencesPlacental Transfer and Pharmacokinetics of a Single Dermal Dose of [14C]Methyl Parathion in Rats
42 Citations2000Aqel W. Abu‐Qare
The results indicate that skin and placenta are poor barriers against methyl parathion permeability, resulting in a rapid and extensive dermal absorption of this insecticide and extensive placental transfer.
TeratologyMaternal toxicokinetics, metabolism, and embryo exposure following a teratogenic dosing regimen with 13‐cis‐retinoic acid (isotretinoin) in the cynomolgus monkey
41 Citations1994Hans Hummler, Andrew G. Hendrickx +1 more
The maternal pharmacokinetics, metabolism, and placental transfer of 13-cis-retinoic acid (isotretinoin) have been determined in the cynomolgus monkey using a dosing regimen which had been previously shown to result in retinoid-specific teratogenic effects.
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40 Citations2004John Kim, K. Wayne Riggs +1 more
FX exhibits extensive stereoselective disposition, which is likely due to differential plasma protein binding of the FX isomers, and there is no detectable fetal formation of NFX, FX, and NFX glucuronides.
Journal of Pharmacology and Experimental TherapeuticsDiethylstilbestrol: placental transfer, metabolism, covalent binding and fetal distribution in the Wistar rat.
40 Citations1982Richard K. Miller, Matthias Heckmann +1 more
It is suggested that fetal tissues may metabolize DES, and both the estrogenic activity of DES and the potential reactivity of its metabolites may be responsible for the toxicity expressed in the fetus.
Antimicrobial Agents and ChemotherapyPharmacokinetics of spiramycin in the rhesus monkey: transplacental passage and distribution in tissue in the fetus
40 Citations1994E Schoondermark-van de Ven, J M Galama +5 more
PubMedLevels of free fatty acids and arachidonic acid in pregnancy and labor.
39 Citations1980Ogburn Pl, Stephen B. Johnson +2 more
Serum levels of total FA and nonesterified AA were measured during normal pregnancies, subsequent labors, and postpartum periods and in cord blood, and the percentage of AA in the total FAs was uniformly lower during labor than at any time during pregnancy.
European Journal of Obstetrics & Gynecology and Reproductive BiologyIn vivo investigation of placental transfer early in human pregnancy
38 Citations2000Eric Jauniaux, Béatrice Gulbis
Because of the slow turn-over of the coelomic fluid, substances such as nicotine to which the mother is chronically exposed accumulate inside the exocoelomic cavity, prolonged fetal exposure to tobacco carcinogens has important teratogenic implications and should be further explored.
Journal of Biological ChemistryRetinol-binding protein synthesis and secretion by the rat visceral yolk sac. Effect of retinol status.
37 Citations1988Dianne Robert Soprano, M L Wyatt +3 more
In the visceral yolk sac, as in the liver, retinol status appears to regulate RBP secretion specifically, without affecting the rate of RBP biosynthesis.
AnesthesiologyToxicity and Distribution of Lidocaine in Nonasphyxiated and Asphyxiated Baboon Fetuses
37 Citations1981Hisayo O. Morishima, Benjamín G. Covino
Results indicate that the increased sensitivity of the asphyxiated fetus to lidocaine may be related in part to a greater uptake of local anesthetics by the fetal organs.
British Journal of AnaesthesiaPLACENTAL TRANSFER OF ORG NC45 IN WOMEN UNDERGOING CAESAREAN SECTION
37 Citations1982M. Demetriou, J.P. Depoix +3 more
It is concluded that Org NC 45 crosses the human placental barrier to a very limited extent and that its use during anaesthesia for Caesarean section is safe for the newborn.
Surgery for Obesity and Related DiseasesVitamin K1 monitoring in pregnancies after bariatric surgery: a prospective cohort study
36 Citations2014Goele Jans, Isabelle Guelinckx +5 more
Low circulating K1 appears to be common in pregnant women with and without bariatric surgery, and Supplementation during pregnancy can restore vitamin K1 in women with bariatrics surgery, potentially protecting the fetus and newborn against intracranial hemorrhage.
American Journal of Obstetrics and GynecologyIn vitro models to predict the in vivo mechanism, rate, and extent of placental transfer of dideoxynucleoside drugs against human immunodeficiency virus
36 Citations1999Tove Tuntland, Aleksandrs Odinecs +3 more
Both in vitro models to predict in vivo placental transfer of drug models resulted in good predictions of the observed fetal/maternal steady-state plasma concentration ratio, which will expedite phase 1 clinical trials of drugs in pregnant women.
Toxicology and Applied PharmacologyPhysicochemical factors in maternal-fetal distribution of drugs
36 Citations1973Roger P. Maickel, Wayne R. Snodgrass
The results indicate that the placental barrier in rats behaves as a lipoidal barrier towards positively charged and neutral drugs, while negatively charged drugs pass the placotional barrier with comparative ease.
Journal of Pharmacology and Experimental TherapeuticsPlacental transfer of valproic acid after liposome encapsulation during in vitro human placenta perfusion.
36 Citations1996Maria Monica Barzago, Angela Bortolotti +6 more
It is indicated that encapsulating VPA in liposomes significantly reduces the fetal amount and exposure, and further in vitro and in vivo investigations are needed to optimize the use of liposome, particularly in pregnancy.
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