Transplacental drug transfer

The degree of exposure of the fetus to a particular substance can be best assessed in human subjects, but concerns of fetal safety have restricted the use of this approach. Moreover, clinical studies cannot elucidate the various mechanisms that contribute to transplacental transport of a particular compound. There are many structural differences between the human placenta and the placenta of other mammalian species, which complicates extrapolation of data obtained from in vivo animal models to humans [7], Thus, several ex vivo and in vitro techniques have been developed to study the placental role in drug transfer and metabolism during pregnancy and there are some excellent articles that discuss these systems in detail [7], Both isolated tissues and various cell culture techniques are currently in use and these have been summarized below. 

Finnegan LP (1979). Pathophysiological and behavioural effects of the transplacental transfer of narcotic drugs to the foetuses and neonates of narcotic-dependent mothers. United Nations Office on Drugs and Crime. Available at http //www.unodc.org/unodc/en/ bulletin/bulletin 1979-01-01 3 page002.html n05... 

Facilitated diffusion is a carrier-mediated mechanism of transplacental transfer. It is important for endogenous substances, such as glucose. It is also the mechanism for some drugs, e.g. the antibiotic cefalexin. Active transport is a carrier-mediated process that requires energy against an electrochemical or concentration gradient. Amino acids and calcium are transported by this mechanism. Only a few drugs, such as a-methyidopa and 5-fluorouracil, are transferred by active transport. 

Transplacental transfer and pharmacokinetics of parathion methyl after dermal application were studied in pregnant rats (Abu-Qare et at., 2000). Both the parent drug and the oxon metabolite were transferred to the fetus, although concentrations were somewhat lower than in maternal tissues. It is clear that the fetus is exposed to a relatively high concentration of parathion methyl even after dermal exposure, and (his exposure leads to a significani degree of cholinesterase inhibition (Abu-Qare and Abou-Donia. 2001) also in placenta tissue (Benjaminov et al., 1992). 

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