Drug Design, Development and Therapy (Jul 2018)
Pharmacokinetics of placental protein 13 after intravenous and subcutaneous administration in rabbits
Abstract
Tijana Drobnjak,1 Hamutal Meiri,2,3 Maurizio Mandalá,4 Berthold Huppertz,5 Sveinbjörn Gizurarson1 1Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Reykjavik, Iceland; 2Hy Laboratories, Rehovot, Israel; 3TeleMarpe Ltd., Tel Aviv, Israel; 4Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy; 5Department of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria Introduction: Human placental protein 13 (PP13) is a galectin predominantly expressed by the placenta. Low serum concentrations of PP13 in early pregnancy indicate a higher risk of developing preeclampsia. Methods: The pharmacokinetic disposition and bioavailability of PP13 were determined by single intravenous and subcutaneous administration to 12 healthy New Zealand White rabbits. The serum pharmacokinetic values were determined by enzyme-linked immunosorbent assay, and are best described by a two-compartment model. Results: Both volume of distribution and the area under the curve were dose dependent for the intravenous group (p<0.01). PP13 elimination half-life was also found to be different between the groups (p<0.01). The bioavailability of PP13 following subcutaneous administration was found to be 57%. Conclusion: This study shows that the concentration of total PP13 released into the maternal circulation during pregnancy might be much higher than previously estimated. Keywords: PP13, ELISA, PK, eNOS, prostaglandin, preeclampsia
