Ampicillin and gentamicin in the treatment of fetal intrauterine infections

Creatsas, G.; Pavlatos, M.; Lolis, D.; Kaskarelis, D

doi:10.1515/jpme.1980.8.1.13

Cited by 18 publications

(3 citation statements)

References 10 publications

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“…At 1-2 h similar drug levels were found in fetal and maternal blood; thereafter, fetal drug levels may exceed maternal levels, possibly because of the rapid elimina tion in maternal blood ( fig. 2, 3) [Bray et al, 1966;Kraybill et al, 1980], It should be noted, that in other studies the fetal levels were reported to remain below maternal levels throughout the observation period (table II) [Williams and Felton, 1966;Hirsch et al, 1974;Creatsas et al, 1980]. The discrepancies between the fetal/matemal concentration ratios reported in the various studies are not easily explained, but may be the result of the influence of different stages of birth and particularly of labor on the pla cental transfer.…”

Section: Transfer Before and During Birthmentioning

confidence: 79%

Clinical Pharmacokinetics in Pregnancy and Perinatology

H¹

1987

Dev Pharmacol Ther

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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.

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Section: Transfer Before and During Birthmentioning

confidence: 79%

Clinical Pharmacokinetics in Pregnancy and Perinatology

H¹

1987

Dev Pharmacol Ther

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“…The study of Weeks et al [28] mentioned a desired target concentration (MIC 0.06 μg/mL) and reported that with their currently used dosing scheme the target concentration will be reached in pregnant women. While Nathan et al [23] mentioned that in only 40% of the pregnant women, the 0.018 μg/mL target concentration was achieved on Day 7 for congenital syphilis. No adapted evidence-based dosing regimen was provided.…”

Section: Benzylpenicillinmentioning

confidence: 99%

“…After oral administration, the C max values reached in non-pregnant women were significant higher than in pregnant women (difference 40.5% points) [22]. Creatsas et al [23] also investigated the effects on C mean , C max and t max of intramuscular administration in pregnant women in their third trimester. The authors found a C max of 7.88 μg/mL in mother's blood 1 h after administration.…”

Section: Ampicillinmentioning

confidence: 99%

Pharmacokinetics and Target Attainment of Antimicrobial Drugs Throughout Pregnancy: Part I—Penicillins

et al. 2023

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Background and Objective Pharmacokinetics (PK) are severely altered in pregnant women due to changes in volume of distribution (Vd) and/or drug clearance (CL), affecting target attainment of antibiotics in pregnant women. This review is part of a series that reviews literature on the description of PK and target attainment of antibiotics in pregnant women with specific focus on penicillins. Methods A systematic literature search was carried out in PubMed. Articles were labelled as relevant when information on PK of penicillins in pregnant women was available. Results Thirty-two relevant articles were included, 8 of which discussed amoxicillin (with and without clavulanic acid), 15 ampicillin, 4 benzylpenicillin, 1 phenoxymethylpenicillin, and 4 piperacillin (with and without tazobactam). No studies were found on pheneticillin and flucloxacillin in pregnant women. Ten out of 32 articles included information on both Vd and CL. During the second and third trimester of pregnancy, a higher CL and larger Vd was reported than in non-pregnant women and in pregnant women during first trimester. Reduced target attainment was described in second and third trimester pregnant women. Only 7 studies reported dosing advice, 4 of which were for amoxicillin. Conclusion The larger Vd and higher CL in second and third trimester pregnant women might warrant a higher dosage or shortening of the dosing interval of penicillins to increase target attainment. Studies frequently fail to provide dosing advice for pregnant women, even if the necessary PK information was available. Key PointsPharmacokinetics (PK) are severely altered in pregnant women due to changes in volume of distribution (Vd) and/or drug clearance (CL), affecting target attainment of antibiotics in pregnant women. This systematic literature review aims to describe the PK and target attainment of penicillins in pregnant women. Volume of distribution and higher CL in second and third trimester pregnant women might warrant a higher dosage or shortening of the dosing interval of penicillins to increase target attainment.

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