Tobramycin: Maternal-Fetal Pharmacology

Bernard, Betty; Garcia-Cázares, Salvador J.; Ballard, Charles A.; Thrupp, Lauri; Mathies, Allen W.; Wehrle, Paul F.

doi:10.1128/aac.11.4.688

Cited by 45 publications

(19 citation statements)

References 9 publications

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“…Data from previous maternal-fetal pharmacokinetic studies indicate that both passive diffusion and receptor-mediated transport are involved in the placental uptake of AGs (6)(7)(8). 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.…”

Section: Introductionmentioning

confidence: 99%

“…If inadequately treated, these infections can lead to serious complications for both the mother and the fetus. Aminoglycoside antibiotics (AGs) are part of the standard treatment regimen for documented and suspected IAIs (4) and are good candidates for intrapartum delivery because they readily cross the placenta and rapidly achieve bactericidal levels in the fetal serum (5)(6)(7)(8). The clinical utility of these antibiotics is limited, however, by their tendency to accumulate in fetal renal tissue after maternal administration and achieve high and persistent levels, even after administration of a single dose.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…Since the majority of our patients received oxytocin to facilitate delivery, the possible effect of this drug should be considered. It is conceivable that this agent may influence the distribution of the drug to the fetus as has been shown to occur when prostaglandins have been used for therapeutic abortions (3). Because of the substantial delivery that did occur to the fetus, however, a significant effect of oxytocin seems unlikely.…”

Section: Resultsmentioning

confidence: 92%

Ceftriaxone distribution between maternal blood and fetal blood and tissues at parturition and between blood and milk postpartum

Kafetzis¹,

Brater²,

Fanourgakis³

et al. 1983

Antimicrob Agents Chemother

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The penetration of ceftriaxone into the fetus at parturition was studied in 17 subjects. Despite its high protein binding, ceftriaxone quickly reached the umbilical cord blood, amniotic fluid, and placenta, achieving substantial concentrations, which then disappeared, with elimination half-lives of approximately 6 h, identical to that of the mother. The elimination half-life of ceftriaxone of 5 to 6 h in these mothers was somewhat shorter than that reported for normal subjects. The concentrations of ceftriaxone achieved in fetal tissues were sufficient for therapeutic effects. The penetration of ceftriaxone into milk was studied 3 days postpartum in 20 other patients. This antimicrobial agent entered breast milk rapidly and disappeared with a half-life of 12 to 17 h. The concentrations achieved were only 3 to 4% of those in maternal serum and were most likely of little clinical relevance.Broad-spectrum cephalosporins could prove to be highly useful for the prophylaxis or treatment of maternal or fetomaternal infections or both (9). Since ceftriaxone has exhibited no serious toxicity in early use and since animal studies indicate no teratogenicity, one may anticipate the use of this drug in pregnancy (9). We, therefore, investigated in 17 subjects the time course of the disappearance of ceftriaxone from the mother and its distribution into the umbilical cord blood, placenta, amniotic fluid, and urine of the neonate. In 20 additional subjects, we assessed the distribution into breast milk.MATERIALS AND METHODS Study protocols. (i) Distribution of ceftriaxone to the fetus. Seventeen healthy women aged 22 to 42 years, at 38 to 41 weeks of gestation, volunteered for this phase of the study after giving informed consent. These patients were hospitalized for the premature rupture of membranes. All were in active labor. Delivery was induced by an intravenous infusion of oxytocin in 13 patients. Caesarean section was performed in four. Each patient received 2.0 g of ceftriaxone dissolved in a total volume of 20 ml of sterile water as an intravenous bolus over 2 to 5 min. The interval from dosing to tissue sampling was determined by the time of expulsion or of removal of the fetus. The characteristics of this group are shown in Table 1. Maternal and umbilical cord blood, placenta samples, and an aliquot of amniotic fluid were collected immediately after delivery. Placenta samples were extensively washed in sterile normal saline, weighed, and homogenized in a Colwarth Stomacher 80 with a triple weight in up to 3 ml of Sorensen buffer, pH 7.2. In addition, in five newborn infants, the first voided urine was collected for analysis.(Ui) Penetration of ceftrlaxone into milk. Twenty healthy mothers aged 19 to 34 years, who had been breast feeding for the 2 preceding days, participated in the study after giving informed consent. On day 3 postpartum, a 1.0-g dose of ceftriaxone in a volume of 10 ml was administered by intravenous bolus over 2 to 5 min to 10 mothers and by intramuscular injection in a volume of 4 ml to the remaini...

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“…In addition, we have demonstrated the ability of the midtrimester fetal kidney t o concentrate and excrete the drug. Concentration of tobramycin, an antibiotic which is structurally related t o gentamicin, b y the human midtrimester fetal kidney has been reported recently (2).…”

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

confidence: 99%

“…However, its frequent association with generalized muscle weakness suggests that interference with transmission of impulses in the neuromuscular junction may play a role. The neuromuscular junction in normal full term and large preterm infants operates with diminished reserves (6, lo), and in some respects resembles that of adult myasthenia gravis (2).…”

Section: Extractmentioning

confidence: 99%

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

1975

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Tobramycin: Maternal-Fetal Pharmacology

Cited by 45 publications

References 9 publications

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

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

Ceftriaxone distribution between maternal blood and fetal blood and tissues at parturition and between blood and milk postpartum

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

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