title: Transfer of lidocaine and bupivacaine across the isolated perfused human placenta.
abstract: Drug permeability and pharmacokinetics through the placenta are important factors determining foetal drug exposure. The purpose of the present 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-hour 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 maternal 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 maternal circulation than lidocaine. At 2 hr, bupivacaine foetal:maternal concentration ratio was 0.56 +/- 0.12 and 14.6% +/- 2.99 of the total circulating amount was found in the foetal circulation. Lidocaine concentration increased more in the foetal circulation and the foetal:maternal 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 foetal 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. Both amide local anaesthetics crossed the dually perfused human placenta rapidly. Bupivacaine disappeared faster than lidocaine from the maternal circulation but less was transferred to foetal circulation. This difference is probably explained by the greater lipophilicity of bupivacaine and hence higher placental binding. These results suggest less foetal drug exposure with bupivacaine than lidocaine.
authors.affiliation: Department of Anaesthesiology, Medical Faculty, University of Oulu, Finland.
authors.forename: T I
authors.initials: TI
authors.lastname: Ala-Kokko
authors.forename: P
authors.initials: P
authors.lastname: Pienimäki
authors.forename: R
authors.initials: R
authors.lastname: Herva
authors.forename: A I
authors.initials: AI
authors.lastname: Hollmén
authors.forename: O
authors.initials: O
authors.lastname: Pelkonen
authors.forename: K
authors.initials: K
authors.lastname: Vähäkangas
mesh_terms: D000779:Anesthetics, Local / Q000378:metabolism* / Q000493:pharmacokinetics; D000983:Antipyrine / Q000378:metabolism / Q000493:pharmacokinetics; D002045:Bupivacaine / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008012:Lidocaine / Q000378:metabolism* / Q000493:pharmacokinetics; D008431:Maternal-Fetal Exchange; D010101:Oxygen Consumption; D010313:Partial Pressure; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012015:Reference Standards
chemical_list: D000779:Anesthetics, Local; D008012:Lidocaine; D000983:Antipyrine; D002045:Bupivacaine