Rifampin 약물명분류연구결과참고문헌 관련된효소, 수송체 등 약동학적지표 OATP1B1 (organic anion-transporting polypeptide 1B1) - The biliary execretion of rifampin occurs after hepatocellular uptake, which is mediated primarily by OATP1B1. 1) 1) Antimicrob Agents Ethnic group Korean Japanese Chinese Caucasian Multiethnicity OATP1B1 Genotype c.463c>a CC c.463c>a CA Dose (n) 1) Multiple dose (71) 1) Multiple dose (15) C max (mcg/ml) (±SD) : 8.8 (4.8) (±SD) : 6.3 (4.5) a T 1/2 (hr) No data CL/F AUC (ng hr/ml) (±SD) : 15.1 (7.9) (±SD) : 26.1 (15.7) b (±SD) : 49.4 (24.0) (±SD) : 29.9 (16.6) c a. p=0.03 b. p=0.0009 c. p=0.0002 Chemother 55: 4122, 1) Antimicrob Agents Chemother 54: 4192, 2010 Rifampin Comments 1) OATP1B1 c.463c>a genotype 과 rifampin 의 PK parameter 간유의한상관관계가있음을알수있다. Comments 1. OATP1B1 rs41490932 genotype의 mutant type인경우에대해, recommended dose보다증량시킨결과 wild type과비슷한 C max 가관찰된연구결과가있다. 1) Antimicrob Agents Chemother 55: 4122, 약력학적지표 Ethnic group Korean Japanese Chinese Caucasian Comments Genotype Treatment (n) Subjects Results No data 1) Comments 1. 외국의허가사항 반영사례 미국 (FDA) 유럽 (EMEA) 일본 (PMDA)
< 약물유전형과관련된약물상호작용 > 1. RSE, relative J Infect Dis standard error 209: 399, Efavirenz Cambodian CYP2B6, NAT2 Efavirenz 600 mg daily in the evening, isoniazid 4-5 rifampicin 10 mg/kg/d 결핵과 HIV 에 모두감염된성 인환자 slow, slow NAT2 metabolizers rapid, rapid NAT2 metabolizers 2014 (exert from table) - Rifampicin은 CYP2B6를유도하며, isoniazid은여러 CYP450을저해하는것으로알려져있으며, NAT2 (N-acetyltransferase type 2) 는 isoniazid의체내노출에관여한다. - Efavirenz의단독투여와항결핵제와의병용투여에대해 CYP2B6와 NAT2의유전형별로살펴본결과, CYP2B6 516GG 군에서단독투여에비해병용투여시 CL/F는 NAT2 slow metabolizer에서 10% 감소하였으며, NAT2 fast metabolizer에서 24% 증가하였으며, CYP2B6 516TT 군에서단독투여에비해병용투여시 CL/F는 NAT2 slow metabolizer에서 16% 감소하였으며, NAT2 fast metabolizer에서 8% 증가하였다. Aids 25: 388, 결핵이아니거 나또는결핵으 Efavirenz? CYP2B6 516G>T Efavirenz 600 mg, rifampin 로인해 rifampin을포함한치료를받고있는 HIV 감염환자들
- CYP2B6 c.516g>t 유전형에대해 efavirenz 와 rifampin 을병용투여한환자군과 efavirenz 만투여한환자군의 efavirenz 혈중농도를비교한결과, CYP2B6TT 유전형이 고 rifampin 을투여한경우가그렇지않은경우보다 2.44 배높은것으로관찰되었으며 (14689 vs. 6012 ng/ml, p=0.006), 그외의다른유전형에서는 rifampin 의투여 여부가유의한영향을미치지않은것으로관찰됨. 2. Indian J Pharmacol Phenytoin Indian (?) CYP2C9 Phenytoin 500 mg, rifampicin 10 isoniazid 5 pyrazinamide 25 ethambutol 15 mg/kg/d 항결핵요법 (anti-tuberulosis therapy, ATT) 을받고있는환자들 44: 485, 2012
- Phenytoin을포함한항결핵요법이 CYP2C9에미치는영향을보기위해 CYP2C9 probe drug으로 phenytoin을병용투여한임상연구임. - 한달의항결핵요법전후로 phenytoin의혈중농도를살펴본결과, CYP2C9*1/*1군의한달후 phenytoin의혈중농도는 33% 로유의하게감소하였으며 (p<0.001), phenytoin의 metabolic ratio역시유의하게감소하였으며 (p<0.05), CYP2C9*2 또는 *3 allele carriers에서도 phenytoin의 metabolic ratio가유의하게감소하였음이관찰됨. < 약물유전형과관련된약물상호작용의국내외의의약품허가사항 > PharmGKP 기재사항 약물유전형과관련된약물상호작용의정보가기재되지않음. KFDA 1. 다음환자에는투여하지말것. 4) 인디나비르, 사퀴나비르, 넬피나비르, 암프레나비르를투여중인환자 FDA CONTRAINDICATIONS Rifampin is contraindicated in patients who are also receiving atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir due to the potential of rifampin to substantially decrease plasma concentrations of these antiviral drugs, which may result in loss of antiviral efficacy and/or development of viral resistance. Rifampin과 atazanavir, darunavir, fosamprenavir, saquinavir, tipranavir를병용투여하면해당약물들의혈중농도가감소하여항바이러스효과및 / 또는바이러스내성이
생길수있으므로병용투여는금기이다. EMA (www.medicines.org.uk/emc) 4.3 Contraindications Rifadin is contra-indicated in patients who: are concurrently receiving saquinavir/ritonavir therapy. Saquinavir/ritonavir 를투여중인환자에게병용투여는금기이다. PMDA 병용금기약물 : HIV 감염치료제 indinavir, saquinavir, nelfinavir, fosamprenavir, atazanavir 임상증상과조치방법 : 해당약물의작용이감약될수있다. 기전, 위험요인 : 본제의 CYP3A4 유도작용에의해해당약물또는활성대사체의대사를촉진하고혈중농도를 1/5 이하로저하시키는것으로생각되고있다.