Placental Transfer of Gentamicin

Yoshioka, Hajime; Monma, Tadao; Matsuda, Sadayuki

doi:10.1097/00006254-197207000-00006

Cited by 10 publications

(15 citation statements)

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“…The partition of gentamicin between human maternal and midtrimester fetal serum observed in this study is similar t o that reported in term infants by Yoshioka (14). In addition, we have demonstrated the ability of the midtrimester fetal kidney t o concentrate and excrete the drug.…”

Section: Discussion Of Venicillin G In Goats Also Does Not Correlate supporting

confidence: 89%

Placental Transfer and Fetal Urinary Excretion of Gentamicin during Constant Rate Maternal Infusion

1975

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Section: Discussion Of Venicillin G In Goats Also Does Not Correlate supporting

confidence: 89%

Placental Transfer and Fetal Urinary Excretion of Gentamicin during Constant Rate Maternal Infusion

1975

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“…In our study, cells were incubated with gentamicin concentrations that are almost 1000-fold higher than what the placenta would be exposed to in clinical settings (8,(12)(13)(14). While these levels would seem clinically irrelevant, they provide a proof of concept.…”

Section: Discussionmentioning

confidence: 99%

“…The administration of 40 and 80 mg of intramuscular gentamicin during labor resulted in peak cord serum levels that were 34% (12) and 42% (13) of associated maternal blood concentrations within 1-2 h, respectively. In the first study (12), the peak maternal serum concentrations (3.7±0.5 μg/mL) were achieved after 30 min of administration, while the peak cord levels of 1.25 μg/mL±0.15 were achieved within 60-120 min. In the latter (13), the maternal serum peak level was 2 μg/mL while the cord levels were ∼0.8 μg/ mL and reached 90 min from administration.…”

Section: Introductionmentioning

confidence: 96%

The Role of Megalin in the Transport of Gentamicin Across BeWo Cells, an In Vitro Model of the Human Placenta

Akour

Kennedy

Gerk

2015

AAPS J

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Abstract. Aminoglycosides (AG) are known to readily cross the placenta, although the mechanisms responsible for placental transport have not been characterized. Megalin is expressed in human placenta, and it is reasonable to speculate, given its role in renal AG uptake, that it is similarly involved in placental transport. However, the role of megalin in placental AG uptake has not been established. An in vitro model to study megalin-mediated placental transport has also not been previously described. The objectives of this study, therefore, were to evaluate the human choriocarcinoma (BeWo) cell line as a model to study megalin-mediated placental transport and to assess the uptake kinetics of gentamicin, an AG antibiotic, using this in vitro model. BeWo cells were grown on Transwell® plates, and megalin expression and functional activity were assessed. Uptake of 3 H-gentamicin was also evaluated in the presence and absence of megalin inhibitors. Expression of megalin protein and mRNA in BeWo cells were confirmed via immunoblot and qPCR analysis. Uptake of fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (BSA) (a megalin substrate) was time-, concentration-, and temperature-dependent consistent with a transporter-mediated process. FITC-BSA uptake was also significantly reduced in the presence of unlabeled gentamicin (a megalin substrate) and sodium maleate (to induce megalin shedding) suggesting that megalin is functionally active in BeWo cells. Gentamicin uptake exhibited time and temperature dependence, saturability and Michaelis-Menten kinetics, all of which suggest a transporter-mediated process. Gentamicin uptake was also significantly reduced in the presence of the megalin inhibitors RAP and EDTA suggesting that megalin is likely involved in gentamicin uptake.

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“…The presence of gentamicin in the plasma of fetuses removed after the mothers had been injected with this drug indicated that, as in humans (5,14,16), the drug crosses the placenta in guinea pigs. However, in guinea pigs, the highest concentration measured in the fetal plasma was about 30 times smaller than that measured in maternal plasma, whereas in humans, cord blood gentamicin concentrations are about one-third those of maternal serum gentamicin concentrations (5,14,16).…”

Section: Discussionmentioning

confidence: 99%

“…Like many other drugs, these compounds are known to cross the human placenta (5,14,16). It is well established that, in adult human and animal kidneys, aminoglycosides accumulate and are nephrotoxic, but in the fetus, their behavior has received little attention.…”

mentioning

confidence: 99%

Kinetics of gentamicin in plasma of nonpregnant, pregnant, and fetal guinea pigs and its distribution in fetal tissues

Lelièvre-Pégorier¹,

Sakly²,

Meulemans³

et al. 1985

Antimicrob Agents Chemother

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Nonpregnant and pregnant guinea pigs in the last third of gestation were injected intramuscularly with 4 mg of gentamicin per kg, and drug concentrations in plasma were determined by radioimmunoassay at several intervals after injection. The maximum gentamicin concentration was significantly lower in pregnant than in nonpregnant animals (14.6 ± 0.7 ,ug/ml versus 21.6 ± 0.7 ,ug/ml), and the peak time occurred significantly later (0.57 ± 0.12 h versus 0.13 ± 0.02 h). Four hours after gentamicin injection, drug concentrations in plasma were 2.1 ± 0.8 and 0.3 ± 0,1 ,ug/ml in pregnant and nonpregnant animals, respectively. Pregnant animals therefore eliminated the drug from their plasma more slowly. These data provide good evidence that the kinetics of plasma gentamicin varies in pregnant females because its volume of distribution was larger in pregnant than in nonpregnant animals. Detectable but small amounts of gentamicin (c 0.50 ,zg/ml) were found in the plasma of 46 of 57 fetuses. However, no net variations in these concentrations were observed during the period between 15 min and 6 h after injection to the mother. Gentamicin concentrations were also determined in the kidneys, liver, lungs, heart, and brain of fetal guinea pigs after administration to their mothers of one daily injection of 4 mg/kg for 7 days. Gentamicin was present in all these fetal organs; however, as in the adult organs, the kidneys contained far more than any of the others. Gentamicin concentrations were not significantly different in the kidney cortex and medulla (1.79 ± 0.16 versus 1.48 + 0.92 ,Lg/g), indicating that, contrary to what is observed for adults, renal accumulation of gentamicin in the fetus does not occur preferentially in the cortex.

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Placental Transfer of Gentamicin

Cited by 10 publications

References 0 publications

Placental Transfer and Fetal Urinary Excretion of Gentamicin during Constant Rate Maternal Infusion

Placental Transfer and Fetal Urinary Excretion of Gentamicin during Constant Rate Maternal Infusion

The Role of Megalin in the Transport of Gentamicin Across BeWo Cells, an In Vitro Model of the Human Placenta

Kinetics of gentamicin in plasma of nonpregnant, pregnant, and fetal guinea pigs and its distribution in fetal tissues

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