표제지
목차
보고서 요약문 6
Summary 7
정책연구용역사업 연구결과 8
제1장 최종 목표 8
1.1. 연구배경 및 목표 8
1.2. 목표달성도 및 관련분야에 대한 기여도 12
제2장 국내외 기술 현황 14
2.1. 프리마퀸 처방이 당면한 문제점 14
2.2. 프리마퀸을 대상으로 한 연구개발 필요성 14
제3장 최종 연구내용 및 방법 16
3.1. 프리마퀸 약동학 연구 16
3.2. LC-MS를 이용한 프리마퀸 대사체 농도 측정 17
3.3. 프리마퀸 약동학 지수 결정 18
3.4. 통계학적 유의성 검증 18
제4장 최종 연구결과 19
4.1. 프리마퀸 약동학를 위한 임상시험 19
4.2. LC-MS를 이용한 프리마퀸 대사체 농도 측정 19
4.3. 프리마퀸 대사체의 약동학 분석 27
제5장 연구결과 고찰 및 결론 35
제6장 연구성과 및 활용계획 43
6.1. 연구성과 43
6.2. 활용계획(연구사업 종료 후) 44
제7장 정책연구용역사업 진행과정에서 수집한 해외과학 기술정보 46
제8장 기타 중요변경사항 47
제9장 연구비 사용 내역 및 연구원 분담표 48
9.1. 연구비 사용 내역(작성일까지 사용내역 작성) 48
9.2. 연구분담표 49
제10장 참고문헌 50
제11장 첨부서류 53
Table 1. Pharmacokinetic parameters of primaquine in the plasma of healthy Korean volunteers after oral administration of primaquine (7.5 mg, 15 mg, and 30 mg) 28
Table 2. Pharmacokinetic parameters of primaquine in the blood cells of healthy Korean volunteers after oral administration of primaquine (7.5 mg, 15 mg, and 30 mg) 28
Table 3. Pharmacokinetic parameters of carboxyprimaquine in the plasma of healthy Korean volunteers after oral administration of primaquine (7.5 mg, 15 mg, and 30 mg) 29
Table 4. Pharmacokinetic parameters of carboxyprimaquine in the blood cells of healthy Korean volunteers after oral administration of primaquine (7.5 mg, 15 mg, and 30 mg) 29
Table 5. Comparison of primaquine pharmacokinetic parameters obtained in this study and other previous reports 39
Table 6. Comparison of carboxyprimaquine pharmacokinetic parameters obtained in this study and other previous reports 40
Fig. 1. Estimated deaths from malaria 8
Fig. 2. Annual incidence of Plasmodium vivax malaria in Republic of Korea (total, civilians and imported cases) 9
Fig. 3. Antimalarial drugs and their target stages 11
Fig. 4. Detection of primaquine by LC-MS/MS analysis 19
Fig. 5. Detection of carboxyprimaquine by LC-MS/MS analysis 20
Fig. 6. Detection of carboxyprimaquine by LC-MS/MS analysis 20
Fig. 7. Calculation of areas under the peak to estimate concentration of target compounds 21
Fig. 8. LC MS/MS standard curves for the quantification of primaquine and carboxyprimaquine in clinical samples 21
Fig. 9. A representative example of mass peak obtained during LC-MS/MS analysis of clinical samples 22
Fig. 10. Plasma concentrations of primaquine versus time following oral administration of 7.5 mg primaquine 23
Fig. 11. Plasma concentrations of carboxyprimaquine versus time following oral administration of 7.5 mg primaquine 23
Fig. 12. Plasma concentrations of primaquine versus time following oral administration of 15 mg primaquine 24
Fig. 13. Plasma concentrations of carboxyprimaquine versus time following oral administration of 15 mg primaquine 24
Fig. 14. Plasma concentrations of primaquine versus time following oral administration of 30 mg primaquine 24
Fig. 15. Plasma concentrations of carboxyprimaquine versus time following oral administration of 30 mg primaquine 25
Fig. 16. Concentrations of primaquine in blood cells versus time following oral administration of 7.5 mg primaquine 25
Fig. 17. Concentrations of carboxyprimaquine in blood cells versus time following oral administration of 7.5 mg primaquine 25
Fig. 18. Concentrations of primaquine in blood cells versus time following oral administration of 15 mg primaquine 26
Fig. 19. Concentrations of carboxyprimaquine in blood cells versus time following oral administration of 15 mg primaquine 26
Fig. 20. Concentrations of primaquine in blood cells versus time following oral administration of 30 mg primaquine 27
Fig. 21. Concentrations of primaquine in blood cells versus time following oral administration of 30 mg primaquine 27
Fig. 22. Comparison of Cmax of primaquine (PQ) and carboxyprimaquine (CPQ) determined in plasma and blood cells, respectively (P values of a-e, a-i, c-g, c-k, d-l 〈 0.017) 31
Fig. 23. Comparison of AUC24 of primaquine (PQ) and carboxyprimaquine (CPQ) determined in plasma and blood cells, respectively (P values of a-e, a-i, b-j, c-g, c-k, d-l 〈 0.017) 31
Fig. 24. Comparison of AUMC∞ of primaquine (PQ) and carboxyprimaquine (CPQ) determined in plasma and blood cells, respectively (P values of a-e, a-i, b-j, c-g, c-k 〈 0.017) 32
Fig. 25. Comparison of MRT of primaquine (PQ) and carboxyprimaquine (CPQ) determined in plasma and blood cells, respectively (P values of c-g, c-k 〈 0.017) 32
Fig. 26. Comparison of Vd/kg of primaquine (PQ) and carboxyprimaquine (CPQ) determined in plasma and blood cells, respectively (P values of b-j 〈 0.017) 33
Fig. 27. Comparison of CL/kg of primaquine (PQ) and carboxyprimaquine (CPQ) determined in plasma and blood cells, respectively 33
Fig. 28. Comparison of T1/2 of primaquine (PQ) and carboxyprimaquine (CPQ) determined in plasma and blood cells, respectively (P values of b-j, c-g, c-k 〈 0.017) 34