At the International Society for the Study of Xenobiotics (ISSX) conference in September 2021, Quotient Sciences [1] and ObsEva [2] presented a scientific poster describing a 14C open-label, two-part radiolabeled study in female subjects to assess the absorption and disposition of nolasiban after oral and intravenous (IV) administrations and to determine the mass balance, routes and rates of metabolism and excretion, and absolute bioavailability.
Nolasiban is an orally active oxytocin receptor antagonist being developed by ObsEva to enhance the receptivity of the endometrium to embryo implantation.
The radiolabeled drug product was manufactured in a GMP (Good Manufacturing Practice) suite co-located with the clinical pharmacology unit. Cohort 1 received a single oral dose of 14C-nolasiban. Total radioactivity analysis was performed on blood, plasma, urine, and feces samples. Plasma samples were analyzed for nolasiban. Cohort 2 received a single oral dose of nolasiban followed by an IV infusion of 14C-nolasiban. Plasma samples were analyzed for nolasiban and 14C-nolasiban.
Mass balance data showed that a mean of 94% of the administered radioactivity was recovered over the 240-hour sampling period. Renal elimination was found to be the main route of elimination. The absolute bioavailability of nolasiban was evaluated to be 77.4%. The proposed metabolic pathway for nolasiban was characterized by oxidation (hydroxylation) and conjugation with glucuronic acid.
Overall, the integration of the radiolabeled human IV microtracer, mass balance, and metabolism study was an efficient and effective method to understand the human drug disposition of nolasiban.
Poster authors:
1. Quotient Sciences: I Shaw, S Sidhu
2. ObsEva: L Marchand, J-P Gotteland
3. Ex-ObsEva: O Pohl
4. Pharmaron-UK: R Cooke