Figure 6.

Levels of OXE receptor antagonists and their major metabolites in plasma following oral administration. OXE receptor antagonists were administered to cynomolgus monkeys by oral gavage as described in Section 2. Blood samples were collected after various times, and the plasma was subjected to solid‐phase extraction, and the amounts of unmetabolized antagonist (●) along with their major plasma metabolite (○) were measured by RP‐HPLC, using appropriate internal standards as shown in Figure 5. Data for S‐C025 (5 mg·kg⁻¹; n = 3), taken from a previous study (Chourey et al., 2018), are shown in panel (a). (b) S‐70 (p‐fluoro; 5 mg·kg⁻¹; n = 1); (c) S‐71 (o‐methoxy; 5 mg·kg⁻¹; n = 2); (d) S‐Y048 (m‐chloro; 5 mg·kg⁻¹; n = 3); (e) S‐Y048 (5 mg·kg⁻¹ followed 8 hr later by a second dose of 5 mg·kg⁻¹); (f) S‐Y048 (2 mg·kg⁻¹ followed 8 hr later by a second dose of 2 mg·kg⁻¹). In two animals, measurements of S‐Y048 and S‐Y048M (M) were made up to 72 hr for doses of S‐Y048 of 5 mg·kg⁻¹ (g) and 2 × 2 mg·kg⁻¹ (h)