To investigate the maternal-fetal transfer of tobramycin (TBM) and its distribution in the fetus, a single dose of 2 mg/kg was administered intramuscularly to 35 pregnant patients (13 first trimester, 22 second trimester) 0.5 to 34 h before hysterectomy. TBM concentration was assayed microbiologically in maternal serum, fetal tissues (placenta, brain, lung, liver, and kidney), and fluids (amniotic, cerebrospinal fluid [CSF], urine, and serum). Mean maternal serum half-life (1.54 h) and mean peak serum concentration ofTBM were within ranges reported for nonpregnant adults. In fetal serum, half-life was 5.2 h, and TBM levels did not exceed 0.58 ,g/ml. For intervals up to 34 h, the mean TBM concentration in placental tissues was 1.4 gg/g. Concentration differences related to fetal maturation were found for fetal CSF, amniotic fluid, and fetal kidney. No antimicrobial activity was found in the fetal CSF of >16 weeks' gestation. TBM was present predominantly in the second trimester amniotic fluid specimens. Fetal kidney concentrations reached 7.2 ug/g at 34 h after maternal drug administration. Higher TBM concentrations were related to advanced maturation ofthe fetal kidney. Second trimester fetal urine concentrations for TBM ranged from 0.1 to 3.4 gg/ml, and the fetal urinary half-life was 3.7 h. Knowledge of fetal pharnacology is essential for weighing the fetal benefits or risks of antimicrobial therapy for the infected gravid patient.
To evaluate maternal-fetal pharmacology of cefatrizine (BL-S 640), a new oral cephalosporin, a single oral 1,000-mg dose was administered to 33 gravidas (8 to 20 weeks' gestation) at varying intervals within 46 h of an elective therapeutic abortion by hysterectomy or intra-amniotic prostaglandin F 2a induction. Mean maternal serum concentrations at 1, 2, 4, and 8 h were 3.7, 7.9, 6.5, and 1.6 μg/ml; beyond a 3-h peak, a half-life of 2.4 h was determined. Cefatrizine placental half-life was 4.4 h. None of the 11 fetuses from a prostaglandin F 2a abortion revealed cefatrizine activity; in contrast, 17 of 22 fetuses from a surgical abortion demonstrated cefatrizine concentrations in two or more samples. Fetal cefatrizine levels were less than 3 μg/g or μg/ml in kidney and urine, less than 2 μg/ml in serum and bile, and less than 2.5 μg/g in lung. After a single maternal dose, cefatrizine has a wide distribution in the fetus in the first half of gestation.
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