Transplacental passage of methicillin and dicloxacillin into the fetus and amniotic fluid

Depp, Richard; Kind, A; Kirby, William M. M.; Johnson, Wayne L.

doi:10.1016/0002-9378(70)90628-9

Cited by 44 publications

(18 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Amniotic fluid levels were rather low in the few samples examined. A slow increase of methicillin in amniotic fluid, as observed with other antimicrobials, was also observed for methicillin by Depp et al [1970], Maternal concentrations prior to the onset of labor were lower than those of nonpregnant adults.…”

Section: Methicillinsupporting

confidence: 58%

“…Since the initial fetal drug level was already the highest fetal level measured, these data would indicate a rapid initial placental transfer to a fetal deep compartment. Depp et al [1970], on the other hand, found fetal/maternal concentration ratios which remained very low throughout the observation period of 8 h. These latter data indicate that the placental transfer of dicloxacillin was slow and the fetus did not act as a deep compartment (fig. 6).…”

Section: Isoxazolyl Penicillinsmentioning

confidence: 70%

“…The authors proposed that the high protein binding of dicloxacillin limited its placental transfer because the low concentrations of free antibi otic decreased the gradient responsible for diffusion across the placenta. If this is indeed the case, then low fetal/maternal concentration ratios should be present at all times as reported in the study of Depp et al [1970]. The question remains, however, why other substances which are extensively bound to plasma proteins (such as benzodiazepines) are transported very rapidly and extensively across the placental membranes.…”

Section: Isoxazolyl Penicillinsmentioning

confidence: 86%

“…An interesting comparison between the placental transfer of methicil lin and dicloxacillin was made by Depp et al [1970]. Methicillin was found to pass from the maternal into the fetal circulation and also into amniotic fluid much more rapidly and extensively than did dicloxacillin ( fig.…”

Section: Methicillinmentioning

confidence: 99%

See 3 more Smart Citations

Clinical Pharmacokinetics in Pregnancy and Perinatology

H¹

1987

Dev Pharmacol Ther

View full text Add to dashboard Cite

Ampicillin has been most thoroughly studied in regard to placental transfer. Both during the first/second trimester and at term, fetal drug levels rose slowly to reach values similar to those in the maternal circulation 1-3 h after maternal drug administration; thereafter, fetal drug levels exceeded corresponding maternal values. Amniotic fluid levels were low during early gestational periods; during late gestation these levels were significant and even exceeded corresponding maternal values 6-8 h after drug administration. Slow exchange rates and fetal micturation may be responsible for the elevated ampicillin levels during late gestation. Administration via the intramuscular (recommended with 0.5 g every 4-6 h) or intravenous routes, but not by the oral route, resulted in adequate drug levels. Because of increased plasma clearance of ampicillin during pregnancy, a dose increase in pregnant patients may be necessary to obtain adequate drug levels. Amoxillin and azidocillin have been suggested to give effective drug levels even after oral administration, except during labor. The fetal levels of epicillin and benzylpenicillin (Penicillin G) were lower than the corresponding maternal values; amniotic fluid concentrations of these two drugs were elevated during late, but very low during early gestation, similar to the situation with ampicillin. Methicillin and sulbenicillin were effectively transfered across the placenta (similar to ampicillin), while dicloxacillin was not. The low concentrations of dicloxacillin in the fetus and amniotic fluid may be the results of extensive protein binding (>90%) of this drug in maternal blood. Other highly bound penicillins such as cloxacillin and flucloxacillin have not yet been investigated in regard to placental transfer. Excretion of penicillins in human milk was usually very limited. Following therapeutic doses, the mean milk concentrations were 0.1-0.6 pg/ml for amoxicillin, 0.1-0.2 pg/ml for epicillin, about 0.5 pg/ml for sulbactam, 2-2.5 pg/ml for ticarcillin, and 0.1-0.4 pg/ml for aztreonam.

show abstract

Section: Methicillinsupporting

confidence: 58%

Section: Isoxazolyl Penicillinsmentioning

confidence: 70%

Section: Isoxazolyl Penicillinsmentioning

confidence: 86%

Section: Methicillinmentioning

confidence: 99%

See 2 more Smart Citations

Clinical Pharmacokinetics in Pregnancy and Perinatology

H¹

1987

Dev Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…Further, while it is true that 0.1% OAP was the concentration presented to mothers throughout gestation, this may not have been the concentration presented to fetuses. Chemical concentrations may become more dilute (8,9) or even increase by the time they reach the fetus (2,19).…”

Section: Discussionmentioning

confidence: 99%