TRANSFER OF LIDOCAINE AND BUPIVACAINE ACROSS THE ISOLATED-PERFUSED HUMAN PLACENTA

Drug permeability and pharmacokinetics through the placenta are import ant factors determining foetal drug exposure. The purpose of the prese nt study was to establish a perfused human placental cotyledon system to assess the placental transfer of lidocaine and bupivacaine, widely used local anaesthetics in obstetric anaesthesia. Term placentas were obtained immediately after delivery with maternal consent and a two-ho ur recycling perfusion of a single placental cotyledon was performed. Bupivacaine or lidocaine with antipyrine as a reference compound were added to the maternal reservoir and their disappearance from the mater nal circulation and appearance to the foetal circulation were followed in five experiments for each drug. Drug concentrations were measured by gas chromatography. Bupivacaine disappeared more rapidly from the m aternal circulation than lidocaine. At 2 hr, bupivacaine foetal:matern al concentration ratio was 0.56+/-0.12 and 14.6%-2.99 of the total cir culating amount was found in the foetal circulation. Lidocaine concent ration increased more in the foetal circulation and the foetal: matern al concentration ratio at 2 hr was 0.90+/-0.09 (P<0.01), and 22.1%+/-2 .21 (P<0.01) was found in the foetal circulation. The maternal to foet al transfer of bupivacaine and lidocaine were 67.2%+/-0.153 and 98.9%0.07 (P<0.05) of that of freely diffusable antipyrine, respectively Bo th amide local anaesthetics crossed the dually perfused human placenta rapidly Bupivacaine disappeared faster than lidocaine from the matern al circulation hut less was transferred to foetal circulation. This di fference is probably explained by the greater lipophilicity of bupivac aine and hence higher placental binding. These results suggest less fo etal drug exposure with bupivacaine than lidocaine.