KMCRIC

[Interaction]
In an open-label, fixed-sequence, two-period, two-treatment crossover study in healthy volunteers (22 enrolled, 20 completed), co-administration of Ojeok-san decreased the systemic exposure of celecoxib at steady state. The geometric mean ratios ([celecoxib+Ojeok-san]/celecoxib) with 90% CIs were 0.725 (0.620-0.848) for Cmax and 0.885 (0.814-0.962) for AUC during the dosing interval. The reductions in mean Cmax and AUC were greater in CYP2C9 intermediate metabolizers than in normal metabolizers [​1​].

[Expert interpretation]
Ojeok-san reduces exposure to Celecoxib (Cmax by about 28%) by decreasing its absorption, with a greater reduction in CYP2C9 intermediate metabolizers, so dose adjustment may need to be considered during concomitant use.

...-san, 五積散)
Treatment: 1포 14.47 g. 3회/1일. 경구 투여. 단독 4일 투여 후 Celecoxib과 4일간 병용. 최종일에는 오적산 단회 투여

[양약투여조건]
Material: Celecoxib 캡슐 200 mg
Treatment: 200 mg. 1회/1일/4일. 경구 투여 (정상 상태)....

[Interaction]
In a prospective clinical crossover trial validating the Meta-HDI deep-learning prediction, co-administration of Ojeok-san with donepezil (Part B, n=9) increased donepezil exposure at steady state: geometric mean ratios (90% CI) were 1.6 (1.3, 1.9) for Cmax,ss and 1.5 (1.2, 1.9) for AUCtau,ss (Cmax,ss 2.1 -> 3.2 ng/mL; AUCtau,ss 36.8 -> 55.0 h*ng/mL; t1/2,ss 47.1 -> 68.7 h). No adverse drug reactions were reported in the Ojeok-san arm and no serious adverse events occurred. In vitro human liver microsome assays identified falcarinol and glabranin as CYP2D6 inhibitors (IC50 45 uM and 4.5 uM) [​2​].

[Expert interpretation]
Ojeok-san increases systemic exposure to Donepezil approximately 1.5–1.6-fold through inhibition of CYP2D6-mediated metabolism, warranting monitoring during concomitant use."

... 간 microsome 실험에서 falcarinol과 glabranin이 CYP2D6 억제제로 확인되었음 (IC50 각각 45 μM, 4.5 μM) [​2​].

[해석]
오적산은 Donepezil의 CYP2D6 매개 대사 억제를 통해 전신 노출을 약 1.5~1.6배 증가시키므로 병용 시 모니터링이 필요함.
...