Given an abstract from a research paper, your task is to identify and label relationships between chemical compounds and genes mentioned in the abstract.

The relationship type must be one of ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].

Please format your output as a JSON array. Each entry in the array should express a single relation, formatted as ["<Entity_A>", "<RELATION_A_B>", "<Entity_B>"]. If no relations can be found, please output an empty JSON array [].

Abstract:

Almorexant effects on CYP3A4 activity studied by its simultaneous and time-separated administration with simvastatin and atorvastatin. PURPOSE: To characterise further the previously observed cytochrome P450 3A4 (CYP3A4) interaction of the dual orexin receptor antagonist almorexant. METHODS: Pharmacokinetic interactions were investigated (n   =   14 healthy male subjects in two treatment groups) between almorexant at steady-state when administered either concomitantly or 2   h after administration of single doses of simvastatin (40   mg) or atorvastatin (40   mg). RESULTS: Almorexant dose-dependently increased simvastatin exposure (AUC (0-∞)) when administered concomitantly [ geometric mean ratios (90% CI): 2.5 (2.1, 2.9) (100   mg), 3.9 (3.3, 4.6) (200   mg) ], but not C (max) [ 3.7 (3.0, 4.5) for both doses ]. Time-separated administration resulted in relevant reductions of the interaction [ AUC (0-∞): 1.4 (1.2, 1.7) (100   mg), 1.7 (1.5, 2.0) (200   mg); C (max): 1.5 (1.3, 1.9) (100   mg), 1.9 (1.6, 2.4) (200   mg) ]. Similar results were obtained for hydroxyacid simvastatin. Independent of almorexant dose and relative time of administration, AUC (0-∞) and C (max) of atorvastatin increased (ratios ranged from 1.1 to 1.5). AUC (0-∞) and C (max) of o-hydroxy atorvastatin decreased dose-independently [ AUC (0-∞): 0.8 (0.8, 0.9) (100   mg), 0.6 (0.5, 0.6) (200   mg); C (max): 0.3 (0.3, 0.4) (100   mg), 0.2 (0.2, 0.3) (200   mg) ] when atorvastatin was concomitantly administered. C (max) of o-hydroxy atorvastatin slightly decreased (0.8 for both doses) following time-separated administration; AUC (0-∞) was unchanged. CONCLUSIONS: Whereas almorexant increased simvastatin exposure dose- and relative time of administration-dependently, atorvastatin exposure increased to a smaller extent and irrespective of dose and time. This suggests that the observed interaction of almorexant with simvastatin is mainly caused by intestinal CYP3A4 inhibition, whereas the interaction with atorvastatin is more due to hepatic CYP3A4 inhibition.
[["almorexant", "REGULATOR", "CYP3A4"], ["Almorexant", "REGULATOR", "CYP3A4"], ["almorexant", "REGULATOR", "cytochrome P450 3A4"], ["almorexant", "ANTAGONIST", "orexin receptor"]]