Nashimoto Shunsuke, Miyamae Masashi, Higuchi Issei, Kono Michihito, Tada Maria, Atsumi Tatsuya, Sugawara Mitsuru, Takekuma Yoh
Laboratory of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Department of Pharmacy, Hokkaido University Hospital, Sapporo, Japan.
Case Rep Nephrol Dial. 2024 Feb 28;14(1):30-35. doi: 10.1159/000536468. eCollection 2024 Jan-Dec.
Mycophenolate mofetil (MMF), an inactive prodrug of mycophenolic acid (MPA), is an immunosuppressive drug used widely in the treatment of lupus nephritis. In this case report, the area under the blood concentration time curve (AUC) of MPA was significantly decreased by the concomitant use of sacubitril/valsartan.
The patient was a man in his 40s with a diagnosis of lupus nephritis class IVa/c+V. MMF dose was 1.5 g/day at admission, and AUC of MPA on day 14 was 25.1 μg⋅h/mL. Owing to poor blood pressure control, sacubitril/valsartan was initiated at 97/103 mg/day on day 29. On day 37, AUC of MPA was significantly decreased to 8.7 μg⋅h/mL, suggesting drug interaction with the newly initiated sacubitril/valsartan. Sacubitril/valsartan was decreased to 49/51 mg/day, and AUC of MPA on day 67 was 37.6 μg⋅h/mL, achieving the target range. The final MMF dose was set at 1.75 g/day. A possible mechanism of drug interaction between sacubitril/valsartan and MPA involves an organic anion transporting polypeptide (OATP). The inhibition of OATPs by sacubitril may have interrupted the enterohepatic circulation of MPA, resulting in a lower plasma concentration.
Since lupus nephritis is often associated with hypertension, the drug interaction observed in this report may also occur in other cases. However, it is impossible to conclude that the decrease in plasma MPA levels was due to the concomitant use of sacubitril/valsartan, and more cases and basic findings are needed.
吗替麦考酚酯（MMF）是霉酚酸（MPA）的无活性前体药物，是一种广泛用于治疗狼疮性肾炎的免疫抑制药物。在本病例报告中，沙库巴曲/缬沙坦的联合使用使MPA的血药浓度-时间曲线下面积（AUC）显著降低。
患者为一名40多岁男性，诊断为IVa/c+V级狼疮性肾炎。入院时MMF剂量为1.5 g/天，第14天MPA的AUC为25.1 μg⋅h/mL。由于血压控制不佳，在第29天开始使用沙库巴曲/缬沙坦，剂量为97/103 mg/天。在第37天，MPA的AUC显著降至8.7 μg⋅h/mL，提示与新启用的沙库巴曲/缬沙坦存在药物相互作用。沙库巴曲/缬沙坦剂量降至49/51 mg/天，第67天MPA的AUC为37.6 μg⋅h/mL，达到目标范围。最终MMF剂量设定为1.75 g/天。沙库巴曲/缬沙坦与MPA之间药物相互作用的一种可能机制涉及有机阴离子转运多肽（OATP）。沙库巴曲对OATP的抑制可能中断了MPA的肠肝循环，导致血浆浓度降低。
由于狼疮性肾炎常与高血压相关，本报告中观察到的药物相互作用可能在其他病例中也会发生。然而，不能得出血浆MPA水平降低是由于联合使用沙库巴曲/缬沙坦所致的结论，还需要更多病例和基础研究结果。
