Oral Pharmacokinetic Drug-drug Interactions between Amifampridine and Acetaminophen in Rats

• 영문명: Oral Pharmacokinetic Drug-drug Interactions between Amifampridine and Acetaminophen in Rats
• 발행기관: 대한약학회
• 저자명: Jin-Woo Cheong Yeo-Dim Park Dang-Khoa Vo Han-Joo Maeng
• 간행물 정보: 『약학회지』제68권 제2호(2024년), 98~104쪽, 전체 7쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2024.03.30

영문 초록

Amifampridine, the first-line medication for Lambert-Eaton myasthenic syndrome (LEMS), is extensively metabolized by N-acetyltransferase 2 (NAT2). Drug-drug interactions (DDIs) can occur when co-administered with a NAT2 inhibitor and amifampridine. Acetaminophen is a widely used analgesic for mild to moderate pain, which is also known as a NAT2 inhibitor. In this work, we studied the effects of acetaminophen on the amifampridine pharmacokinetics in rats. Both acetaminophen (300 mg/kg) and amifampridine (2 mg/kg) were administered orally. In acetaminophen-treated rats, the systemic exposure to amifampridine significantly increased, and the ratio of the area under the plasma concentration-time curve for 3-N-acetylamifampridine to amifampridine (AUCm/AUCp) decreased markedly, which is likely due to the inhibition of NAT2 by acetaminophen. Also, the urinary amount excreted was increased in the acetaminophen-treated group, but the renal clearance remained unchanged. This oral pharmacokinetic drug-drug interaction study showed that orally administered acetaminophen significantly inhibits the NAT2-based metabolism of amifampridine and may cause meaningful DDIs.

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키워드

Amifampridine N-acetyltransferase 2 (NAT2) Acetaminophen 3-N-acetylamifampridine Drug-drug interactions (DDIs)