Placental transfer and pharmacokinetics of allopurinol in late pregnant sows and their fetuses.
At present no standard pharmacological intervention strategy is available to reduce these adverse effects of birth asphyxia. In the present study we aimed to evaluate placental transfer of allopurinol, an inhibitor of XOR. For this purpose, fetal catheterization of the jugular vein was conducted in five late pregnant sows (one fetus per sow). At 24-48 h after surgery, sows received allopurinol (15 mg/kg body weight; i.v.) and pharmacokinetics of allopurinol and its active metabolite oxypurinol were measured in both late pregnant sows and fetuses. Maternal and fetal blood samples were collected during and after allopurinol administration. Maternal C(max) values averaged 41.90 microg/mL (allopurinol) and 3.68 microg/mL (oxypurinol). Allopurinol crossed the placental barrier as shown by the average fetal C(max) values of 5.05 microg/mL at 1.47 h after allopurinol administration to the sow. In only one fetus low plasma oxypurinol concentrations were found. Incubations of subcellular hepatic fractions of sows and 24-h-old piglets confirmed that allopurinol could be metabolized into oxypurinol. In conclusion, we demonstrated that allopurinol can cross the placental barrier, a prerequisite for further studies evaluating the use of allopurinol as a neuroprotective agent to reduce the adverse effects following birth asphyxia in neonatal piglets.
van Dijk
A J
AJ
Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. a.j.vandijk@uu.nl
Parvizi
N
N
Taverne
M A M
MA
Fink-Gremmels
J
J
D000493:Allopurinol / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D001238:Asphyxia Neonatorum / Q000517:prevention & control*; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008431:Maternal-Fetal Exchange; D008657:Metabolic Clearance Rate; D010117:Oxypurinol / Q000097:blood / Q000627:therapeutic use*; D011247:Pregnancy; D013552:Swine; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D000493:Allopurinol; D014968:Xanthine Dehydrogenase; D010117:Oxypurinol