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Abstract

Placental transfer, tissue distribution, and pharmacokinetics of cyclosporine in the pregnant rabbit.

L Sangalli, A Bortolotti, F Passerini and M Bonati
Drug Metabolism and Disposition January 1990, 18 (1) 102-106;
L Sangalli
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A Bortolotti
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F Passerini
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M Bonati
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Abstract

The disposition of cyclosporine during pregnancy is described for the first time using the pregnant rabbit model. After a detailed kinetic study, in which a 5 mg/kg dose of cyclosporine was used, the apparent tissue-to-blood partition coefficients were determined at steady state in six pregnant rabbits after a two-step infusion of cyclosporine for 8 hr at a mean arterial blood concentration of 1.25 mg/liter, detected by HPLC. Muscle and fat were major drug deposits, and the maternal kidney--site of considerable side effects--accumulated the highest concentration of the drug. Spleen, mammary gland, liver, lung, heart, bile, and adrenal gland showed intermediate ability to accumulate the drug. The whole fetus accumulated little cyclosporine, and the drug was not detectable in maternal and fetal brains and in the amniotic fluid. At delivery, the mean cyclosporine concentration in fetal blood was 0.07 mg/liter, amounting to 6% of the mother's concentration. It would appear that diffusional resistance governs the transfer of cyclosporine into brain and fetus. Although caution obviously must be applied in extrapolating experimental data to clinical situations, the present findings do suggest that: a) exposure of the fetus to cyclosporine is low at a high maternal steady-state concentration; and b) caution should be applied in suggesting breastfeeding by these patients, since cyclosporine was found in a considerable amount in the mammary gland.

 

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Drug Metabolism and Disposition
Vol. 18, Issue 1
1 Jan 1990
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Abstract

Placental transfer, tissue distribution, and pharmacokinetics of cyclosporine in the pregnant rabbit.

L Sangalli, A Bortolotti, F Passerini and M Bonati
Drug Metabolism and Disposition January 1, 1990, 18 (1) 102-106;

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Abstract

Placental transfer, tissue distribution, and pharmacokinetics of cyclosporine in the pregnant rabbit.

L Sangalli, A Bortolotti, F Passerini and M Bonati
Drug Metabolism and Disposition January 1, 1990, 18 (1) 102-106;
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