The rabbit as an animal model to study pharmacokinetics of norethindrone in women

The pharmacokinetics of norethindrone (NET) were studied in adult female rabbits and rhesus monkeys with a view to developing an animal model closely resembling humans in the handling of NET. Plasma levels of NET were determined in rabbits and monkeys after administering either labelled NET or a NET minipill. Pharmacokinetic parameters were evaluated by using a two-compartment open model and by graphical and regression analysis of plasma NET data. In rabbits, the drug absorption was found to be rapid and NET peak levels were attained within 0.5 to 1.0 hour. The clearance half-lives were 1.3 hours for 'alpha' and 10.0 hours for 'beta'. In monkeys, plasma NET values showed an inconsistent pattern and the approximate t 1/2 was found to lie between 4 and 6 hours. The observed pharmacokinetics of NET in rabbits rather than in monkeys were closer to those in humans. On this basis, it would appear that the rabbit is a suitable animal model for studying effects of nutritional factors on the pharmacokinetics of NET.