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Transfer of Ciprofloxacin, Ofloxacin and Levofloxacin Across the Perfused Human Placenta In Vitro

Polachek, Hana; Holcberg, Gershon; Sapir, Gadi; Tsadkin-Tamir, Marina; Polachek, Joseph; Katz, Miriam; Ben-Zvi, Zvi

Obstetrical & Gynecological Survey: February 2006 - Volume 61 - Issue 2 - p 77-78
doi: 10.1097/01.ogx.0000197813.42751.d8
Obstetrics: Physiology & Pathophysiology of Pregnancy, Labor, and the Puerperium

The fluoroquinolones are antibiotic agents that act by inhibiting bacterial DNA gyrase. Because they are able to cross the placenta, they may have mutagenic or carcinogenic effects on the developing fetus. The present in vitro study examined the transfer of 3 therapeutically important fluoroquinolones—ciprofloxacin, ofloxacin, and levofloxacin—through the isolated, perfused human placenta. Placental cotyledons from normal human term placentas were perfused with M199 medium enriched with bovine serum albumin and glucose. Perfusion rates were 12 mL/min in the maternal circulation and 6 mL/min in the fetal circulation. Six placentas were studied for each of the 3 fluoroquinolones after they were added to the maternal circulation. Antipyrine, which crosses the placenta by simple diffusion, served as a reference drug. Concentrations of all agents were measured by high-performance liquid chromatography.

After 30 minutes, antipyrine had reached a steady state in the fetal compartment. The mean transplacental transfer percentage of antipyrine was 10.0% for ciprofloxacin, 13.4% for ofloxacin, and 13.2% for levofloxacin. Ciprofloxacin crossed the placenta, reaching a steady state at 30 minutes in both the maternal and fetal compartments. Ofloxacin and levofloxacin also reached a steady state after 30 minutes. The mean transplacental transfer percent of ciprofloxacin was 3.2% and the transplacental transfer index (the ratio of transplacental transfer between ciprofloxacin and antipyrine) was 0.34. The respective figures for ofloxacin were 3.7% and 0.33, and for levofloxacin, 3.9% and 0.34. The placental transfer of each of the fluoroquinolone drugs was significantly smaller than was observed for antipyrine.

In this in vitro study, only a small proportion of 3 fluoroquinolone drugs passed into the fetal compartment. Possibly there is a barrier to fluoroquinolone transport in the human placenta.

Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Division of Obstetrics and Gynecology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; and Department of Family Medicine, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Eur J Obstet Gynecol Reprod Biol 2005;122:61–65

© 2006 Lippincott Williams & Wilkins, Inc.