티크로피딘이 니칼디핀의 생체이용률 및 약물동태에 미치는 영향

Effects of Ticlopidine on the Bioavailability and Pharmacokinetics of Nicardipine after Oral and Intravenous Administration

  • 문홍섭 (국립목포대학교 약학대학) ;
  • 최준식 (조선대학교 약학대학 & 임상약학대학원) ;
  • 방준석 (조선대학교 약학대학 & 임상약학대학원)
  • Moon, Hong-Seop (College of Pharmacy, Mokpo National University) ;
  • Choi, Jun-Shik (College of Pharmacy & Graduate School of Clinical Pharmacy, Chosun University) ;
  • Bang, Joon-Seok (College of Pharmacy & Graduate School of Clinical Pharmacy, Chosun University)
  • 투고 : 2011.12.30
  • 심사 : 2012.01.30
  • 발행 : 2012.03.31

초록

항혈소판제인 티크로피딘과 항고혈압제인 니칼디핀과의 약동학적 상호작용 연구를 위하여 티크로피딘 (3 또는 10 mg/kg)과 니칼디핀의 경구 (4 mg/kg) 및 정맥 (12 mg/kg) 투여하여 본 연구를 시행하였다. 연구방법: 티크로피딘이 cytochrome P450 (CYP) 3A4 활성과 P-glycoprotein (P-gp)의 활성에 미치는 영향도 평가하였다. 결 과: 티크로피딘과 니칼디핀의 병용투여 시 티크로피딘이 니칼디핀의 약물동태 파라미터에 미치는 결과는 다음과 같다. 티크로피딘은 CYP3A4 효소의 활성을 저해 하였으나 P-gp활성에는 영향을 미치지 못하였다. 니칼디핀의 혈중농도곡선하면적 (AUC)는 대조군에 비해 티크로피딘 10 mg/kg 병용투여군에서 유의성 (p < 0.05)있게 증가되었다. 상대적 생체이용률 (RB)은 티크로피딘 병용투여군에서 115-143%로 증가하였다. 결 론: 본 논문에서 흰쥐에 티크로피딘과 니칼디핀을 병용경구투여 시 니칼디핀의 생체이용률 (bioavailability)이 유의성 (p < 0.05)있게 증가된 것은 티크로피딘이 대사효소인 CYP3A4를 억제하여 소장과 간장에서 초회통과효과 (first-pass metabolism)를 감소 시켰기 때문인 것으로 사료된다. 본 실험결과를 토대로 인체에서 티크로피딘과 니칼디핀의 상호작용을 검토한 후 투여용량을 조절하는 것이 바람직하다고 사료된다.

키워드

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