Transplacental transfer of oseltamivir and its metabolite using the human perfused placental cotyledon model

Berveiller, Paul; Mir, Olivier; Vinot, Cécile; Bonati, Céline; Duchêne, P.; Giraud, C; Gil, Sophie; Tréluyer, Jean‐Marc

doi:10.1016/j.ajog.2011.07.023

Cited by 27 publications

(14 citation statements)

References 27 publications

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“…The transplacental transfer of OC to the fetal circuit (Cl index range 0.2-0.6) utilizing the perfusion system in its closed-closed (re-circulating) mode revealed that it is in agreement with the reported data utilizing the open-open mode of the perfusion system (Cl index range 0.2-0.5) [5]. The re-circulated mode of the perfusion system most closely simulates the in vivo conditions, especially for drugs that do not undergo further biotransformation by maternal, placental, and fetal metabolic enzymes, such as in the case of OC.…”

Section: Discussionsupporting

confidence: 80%

“…Since kidney transporters are important components of active tubular secretion, the interaction of OC with transporters in kidney and other tissues, including placenta is plausible. Also, to the best of our knowledge, there is no published data on the interaction between placental transporters and OC, Berveiller et al does not exclude their role in the observed transplacental transfer of OC [5].…”

Section: Introductionmentioning

confidence: 98%

“…The concentrations of compounds were determined in 0. 5 At the end of experiment, the perfused area was dissected from the adjoining placental tissue, weighed, and homogenized in a volume of saline equal to four times its weight. 1 mL of 1M NaOH was added to 1 mL of the homogenate and the samples were incubated for 12 hours at 60 °C in the dark to allow for luminescence decay.…”

Section: Transplacental Transfer and Distribution Of Ocmentioning

confidence: 99%

“…Indeed, utilizing the technique of dual perfusion of placental lobule (DPPL) and OC in a concentration similar to that in the circulating blood of non-pregnant patients, Berveiller et al demonstrated that OC is transferred to the fetal circuit [5]. On the other hand, Worley et al, utilizing the same experimental technique was unable to detect OC in the fetal circuit following the perfusion of OP in the maternal to fetal direction in the concentration range 5-6 fold above of its therapeutic level [6].…”

Section: Introductionmentioning

confidence: 99%

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604: Transplacental transfer of oseltamivir carboxylate

Patrikeeva

Nanovskaya

et al. 2012

American Journal of Obstetrics and Gynecology

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Objectives-Determine the bidirectional transfer of oseltamivir carboxylate (OC) across term human placenta and its distribution between the tissue, maternal and fetal circuits. Methods-The technique of dual perfusion of placental lobule (DPPL) in its recirculating mode was utilized to determine the transfer of the drug. OC (350 ng/ml) was co-perfused with its [ 3 H]-isotope and the marker compound antipyrine (AP, 20 μg/mL) together with its [ 14 C]-isotope. The concentrations of OC and any of its metabolite(s) formed during perfusion were determined in the tissue, maternal and fetal circuits by liquid scintillation spectrometry following their separation by High Performance Liquid Chromatography (HPLC).Results-The distribution of OC following its perfusion in the Maternal-to-Fetal direction for 4 hours was as follows: 21 ± 4% of the drug was transferred to the fetal circuit, 13 ± 5% was retained by the perfused lobule, and 66 ± 4% remained in the maternal circuit. The normalized transfer of OC to that of AP (Clearance index) in the Maternal-to-Fetal direction was (0.47 ± 0.11) and was not different from its transfer from the Fetal-to-Maternal direction (0.47 ± 0.06) suggesting that involvement of placental efflux transporters is unlikely.Conclusions-OC crosses human placenta. Since the transfer rate of OC is 47% of the freely diffusible AP, it is likely that fetus could be exposed to OC during pregnancy.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 98%

Section: Transplacental Transfer and Distribution Of Ocmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

604: Transplacental transfer of oseltamivir carboxylate

Patrikeeva

Nanovskaya

et al. 2012

American Journal of Obstetrics and Gynecology

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“…Moreover, amniotic fluid may act as a third space for many drugs, as recently documented for dasatinib [5]. Finally, the decrease in albumin level observed during pregnancy may favor the transplacental transfer rate of many drugs, especially highly protein-bound molecules [6]. …”

mentioning

confidence: 99%