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건강한 남성 자원자에서 탐스로신의 공복 투여 시 항정상태의 약동학적 특성 연구

Steady-State Pharmacokinetic Properties of Tamsulosin in Healthy Male Volunteers

  • 성숙진 (경북대학교병원 임상시험센터) ;
  • 이혜원 (경북대학교병원 임상시험센터) ;
  • 이주미 (경북대학교병원 임상시험센터) ;
  • 임미선 (영남대학교 약학대학) ;
  • 김은희 (영남이공대학교 간호대학) ;
  • 박성민 (경북대학교병원 임상시험센터) ;
  • 권미리 (경북대학교병원 임상시험센터) ;
  • 윤영란 (경북대학교병원 임상시험센터)
  • Seong, Sook Jin (Department of Clinical Trial Center, Kyungpook National University Hospital) ;
  • Lee, Hae Won (Department of Clinical Trial Center, Kyungpook National University Hospital) ;
  • Lee, Joomi (Department of Clinical Trial Center, Kyungpook National University Hospital) ;
  • Lim, Mi-Sun (College of Pharmacy, Yeungnam University) ;
  • Kim, Eun Hee (School of Nursing, Yeungnam College of Science & Technology) ;
  • Park, Sung Min (Department of Clinical Trial Center, Kyungpook National University Hospital) ;
  • Gwon, Mi-Ri (Department of Clinical Trial Center, Kyungpook National University Hospital) ;
  • Yoon, Young-Ran (Department of Clinical Trial Center, Kyungpook National University Hospital)
  • 투고 : 2013.11.14
  • 심사 : 2013.12.22
  • 발행 : 2013.12.31

초록

배경: 본 연구는 건강한 한국인 자원자를 대상으로 공복상태에서 5일간 탐스로신을 투여한 뒤 약동학적 특성을 평가하고자 하였다. 방법: 무작위배정, 공개, 반복 투여, 2기 교차 시험 설계로 수행된 본 연구는, 총 44명의 시험대상자를 1:1로 무작위 배정하여 제 1기에 시험약으로 탐수로이신$^{(R)}$ 캡슐 0.2 mg 또는 대조약인 하루날$^{(R)}$ 캡슐 0.2 mg을 각각 투여하고 10일간의 휴약기를 거친 후 제 2기에는 1기와 반대로 해당 임상시험용 의약품을 투여하였다. 탐스로신의 혈장 농도는 HPLC-MS/MS를 사용하여 측정하였다. 안전성 평가를 위하여 임상실험실 검사, 이상반응 모니터링, 신체검진 등을 수행하였다. 결과: 시험약과 대조약의 약동학적 파라미터는 다음과 같았다(평균(표준편차)). $C_{ss,max}$는 시험약이 9.0 (2.9) ng/mL, 대조약은 8.4 (2.6) ng/mL이었고, $t_{max}$(중앙값(최소값-최대값))는 시험약이 4 (2-6), 대조약은 5 (2-7) hours이었다. $AUC_{\tau}$는 시험약이 93.7 (31.5) $ng{\times}h/mL$, 대조약은 88.2 (29.3) $ng{\times}h/mL$이었으며, $t_{1/2}$의 경우 시험약은 9.5 (2.6), 대조약은 10.0 (2.7) hours이었다. 탐스로신 경구 투여 후 volume of distribution 과 clearance는 각각 0.5 L/kg, 0.04 L/h/kg이었고, 탐스로신 0.2 mg 1일 1회 용법에 대한 accumulation ratio는 1.2였다. 로그 변환한 $AUC_{\tau}$$C_{ss,max}$ 변수의 대조약에 대한 시험약의 기하평균비의 90 % 신뢰구간은 각각 1.005-1.131, 1.000-1.136으로 동등성 범위 이내에 속하였다. 시험기간 동안 중대한 이상반응은 발생하지 않았고 시험약과 대조약 모두 내약성이 우수하였다. 결론: 공복상태에서 탐스로신을 투약한 후 $C_{ss,max}$$AUC_{\tau}$는 타 연구에서 음식물과 함께 탐스로신을 복용한 경우보다 증가하였고 tmax는 감소하였다.

Background: To evaluate the pharmacokinetic properties of daily oral doses of tamsulosin administered to fasted healthy Korean male volunteers for 5 days. Methods: In a randomized, open-label, multiple-dose, two-period, crossover study, all 44 subjects were randomly assigned in a 1:1 ratio to receive a newly developed generic capsule formulation (test) or a branded capsule formulation (reference) of tamsulosin 0.2 mg, followed by a 10-day washout period and administration of the other formulation. Plasma concentrations of tamsulosin were assessed after administration of five-day multiple doses, using HPLC-MS/MS. Clinical and laboratory adverse events (AE) were assessed. Results: The mean (SD) pharmacokinetic properties with the test and reference formulations were as follows: $C_{ss,max}$, 9.0 (2.9) and 8.4 (2.6) ng/mL, respectively; median (range) $t_{max}$, 4 (2-6) and 5 (2-7) hours; $AUC_{\tau}$, 93.7 (31.5) and 88.2 (29.3) $ng{\times}h/mL$; and $t_{\frac{1}{2}}$, 9.5 (2.6) and 10.0 (2.7) hours. The volume of distribution and clearance after oral administration of tamsulosin were 0.5 L/kg, and 0.04 L/h/kg, respectively. The accumulation ratios for 0.2 mg once-daily dosing regimen were 1.2. The 90% CIs of the geometric mean ratios for the log-transformed $AUC_{\tau}$ (1.005-1.131) and $C_{ss,max}$ (1.000-1.136) values were within the acceptable range for bioequivalence. No serious AE was reported during the study. Both formulations were well tolerated. Conclusion: The results demonstrate that the $C_{ss,max}$ and $AUC_{\tau}$ values in the fasted subjects were higher than those in the fed from other study, with a shorter $t_{max}$ values.

키워드

참고문헌

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피인용 문헌

  1. Physiologically based pharmacokinetic (PBPK) modelling of tamsulosin related to CYP2D6*10 allele vol.44, pp.11, 2021, https://doi.org/10.1007/s12272-021-01357-z