*1a/*15 Uncut 250
300
200
150
100
*1a/*1a *1a/*5 *5/*5
130 bp 111 bp
2500
1000
500 1500 2000 3000
2280 bp 1814 bp
3.5.4 OATP1B1
OATP1B1
1. OATP1B1 (allele)
(1) OATP1B1*1a OATP1B1
(2) OATP1B1*1b OATP1B1 genomic DNA 388
adenine (A) guanine (G)
(3) OATP1B1*5 OATP1B1 genomic DNA 521
thymine (T) guanine (C)
(4) OATP1B1*15 OATP1B1*1b OATP1B1*5
2. OATP1B1 (genotype) OATP1B1
(1) OATP1B1 OATP1B1
OATP1B1*1a/*1a
(2) OATP1B1 OATP1B1
OATP1B1*1b OATP1B1*5 OATP1B1*15
3. (allele frequency)
4. OATP1B1*5 OATP1B1*5 OATP1B1*15
5. (homozygous genotype) (allele)
3.6
Excel SPSS 13.0 for Windows (continuous and categorical data)
OATP1B1 Pearson Chi-square test
5 Fisher’s exact test OATP1B1
Odds Ratio 95% (confidence interval) (Body mass index BMI)
independent t-test nonparametric
Wilcoxon rank sum test Naranjo Score RUCAM Spearman’s Rho test P<0.05
4
4.1
4.1.1
94 12 1 96 4 30
102 97
5 2 B 3 C
4.1.2
4.1 97 65 (67% 32
(33%) 2 54.8
24 (24.7%) 30 (30.9%) 8
(8.2%) 5 (5.2%) 4 (4.1%)
(42 43.3%)
(24 24.7%) 21 (21.6%) 4 (4.1%)
4 (4.1%)
HERZ
HER 6 6.2%
4.1 (97 )
(Diabetes mellitus) 30(30.9)
(Asthma) 3(3.1)
(COPD) 5(5.2)
(GI-related disease) 8(8.2)
(Renal disease) 3(3.1)
(Liver disease) 4(4.1)
42(43.3)
Rifampin (RIF) mg/kg 10.3±1.7
4.1.3
AST ALT 76 (78.4%)
73 (75.3%) Total bilirubin direct bilirubin ALP
29 (29.9% 10 (10.3%) 6 (6.2%) ( 4.2 4.1)
( ) ( )
AST 76(78.4%) 5-30 U/L 22(9~56)
ALT 73(75.3%) 5-35 U/L 17(7~53)
Total bilirubin 29(29.9%) 0-1.2 mg/dl 0.59(0.23~1.97) Direct bilirubin 10(10.3%) 0-0.4 mg/dl 0.20(0.01~0.04)
ALP 6(6.2%) 50-136 U/L 69(41~138)
%
4.2
4.2
4.2.1
59 (60.8%)
43 (44.3%) 16 (16.5%)
12 (12.3%) 1
(1.0%) 3 (3.2%) 4.2
4.2
4.2.2
CIOMS (
)
12 (12.3%)
16 (16.5%)
38 (39.2%) 43 (44.3%)
1 (1.0%)
3 (3.2%)
Naranjo Score
16 6 (37.5%)
(possible) 6 (37.5%) (probable)
4 (25%) (
(definite)
RUCAM
3 (18.75%) (possible) 7 (43.75%) (probable)
6 (highly probable)
( 4.4) Naranjo Score RUCAM 0.826
(P<0.01)
4.3 Naranjo Score
4.3
4.3.1
( )
16 81
4.5
BMI (
rifampin isoniazid pyrazinamide ethambutol
( 50.7±10.8 kg 56.8±10.2
kg) ethambutol 800mg/qd
ethambutol
4.5
(%) 10(62.5) 55(67.9)
(%) 6(37.5) 26(32.1)
62.4±20.3 53.2±20.5 0.104
(cm) 160.5±10.5 163.8±7.9 0.187
(kg) 50.7±10.8 56.8±10.2 0.048*
(Body mass index, BMI) 19.3±2.8 21.3±3.5 0.055
5(31.25) 19(23.5) 0.354
4(25) 26(32.1) 0.405
1(6.25) 2(2.5) 0.421
5(6.2) 0.398
2(12.5) 6(7.4) 0.392
2(12.5) 1(1.2) 0.07
1(6.25) 4(4.9) 0.602
4(25) 38(46.9) 0.088
2(12.5) 22(27.1) 0.179
6(37.5) 15(18.5) 0.092
4(4.9) 0.48
1(6.25) 3(3.7) 0.52
Rifampin (RIF) mg/kg 10.55±2.58 10.24±1.47 0.175
Isoniazid (INH) mg/kg 6.8±1.16 6.52±1.55 0.505
Pyrazinamide (PZA) mg/kg 17.8±10.03 19.07±7.54 0.755 Ethambutol (EMB) mg/kg 14.87±5.23 11.86±5.43 0.022*
4.3.2
4.6
AST ALT Tbil
AST ALT 10
Tbil (1.2mg/dL) CIOMS
4.6
P value
(N=16) (N=81)
( ) ( )
AST(U/L) 30(13-56) 22(9-52) 0.812
ALT(U/L) 21 (9-42) 16(7-53) 0.271
Total bilirubin(mg/dL) 0.63(0.23-1.1) 0.59(0.24-1.97) 0.82
AST (U/L) 157(37-1680) 29.5(6-159) <0.001
ALT (U/L) 143(54-2285) 22(6-67) <0.001
Total bilirubin
(mg/dL) 0.91(0.6-2.54) 0.76(0.28-2.68) 0.011
4.3.3 OATP1B1
OATP1B1*1a OATP1B1*1b OATP1B1*5 OATP1B1*15
OATP1B1 7 4.7 OATP1B1
OATP1B1
*1a/*5 *15/*15 OATP1B1*5( OATP1B1*5 OATP1B1*15)
OATP1B1*1a
OATP1B1*1a OATP1B1*1a
OATP1B1*1a
(Odds Ratio) 95% (Confidence Interval)
OR 95% CI P value (N=16) (N=81)
(%) (%)
OATP1B1 genotype
OATP1B1*1a/*1a 2(12.5) 4(4.9) 2.75 0.46-16.48 0.257 OATP1B1*1a/*1b 4(25) 26(32.1) 0.71 0.21-2.39 0.405 OATP1B1*1b/*1b 7(43.75) 34(42) 1.08 0.36-3.17 0.554
OATP1B1*1a/*5 1(1.2) 0.835
OATP1B1*1a/*15 2(12.5) 2(2.5) 5.64 0.73-43.43 0.126 OATP1B1*1b/15 1(6.25) 13(16.1) 0.35 0.04-2.88 0.28
OATP1B1*15/*15 1(1.2) 0.835
With *5 3(18.8) 17(21) 0.87 0.22-3.4 0.572
Number of OATP1B1*1a
Two OATP1B1*1a 2(12.5) 4(4.9) 2.75 0.46-16.48 0.257 One OATP1B1*1a 6(37.5) 29(35.8) 1.08 0.36-3.26 0.554
No OATP1B1*1a 8(50) 48(59.3) 0.69 0.24-2.01 0.339
4.7 OATP1B1
4.3.4 OATP1B1
OATP1B1
( 4.8) OATP1B1*5
OATP1B1*5 OATP1B1*15( OATP1B1*1b allele ) OR OATP1B1*1a OATP1B1*1b OATP1B1*15
OATP1B1*5 OR ( 4.12)
4.8 OATP1B1
OR 95% CI P value
(N=32) (N=162)
(%) (%)
OATP 1B1*1a 10(31.35) 37(22.8) 1.54 0.67-3.53 0.31 OATP 1B1*1b 19(59.4) 107(58.8) 0.75 0.35-1.63 0.47
OATP 1B1*5 1(0.5) 0.84
OATP 1B1*15 3(9.4) 17(9.3) 0.88 0.24-3.20 0.57
4.4 OATP1B1
OATP1B1
OATP1B1 6
(6.2% OATP1B1 91 (93.8%)
( 4.9)
OATP1B1 OATP1B1 P value
N=6 N=91
( ) ( )
AST (U/L) 20 (13~26) 29 (9~56) 0.631
ALT (U/L) 17 (11~22) 19 (7~53) 0.398
Total bilirubin (mg/dL) 1.97 ( ) 0.66 (0.23~1.96) *
AST (U/L) 100.8 (19-414) 85.8 (6-1680) 0.857
ALT (U/L) 116.5 (15-511) 86.2 (6-2285) 0.794
Total bilirubin
(mg/dL) 1.3 (0.53-2.68) 0.96 (0.28-2.54) 0.335
*OATP1B1 Total bilirubin P value
4.9 OATP1B1
OATP1B1*5
OATP1B1*5( OATP1B1*5 OATP1B1*15) OATP1B1*5
( 4.10)
OATP1B1*5 OATP1B1*5 P value
N=20 N=77
( ) ( )
AST (U/L) 30 (9~56) 24 (11~50) 0.364
ALT (U/L) 20.1 (7~53) 16.8 (11~29) 0.213
Total bilirubin (mg/dL) 0.69 (0.23~1.97) 0.81 (0.32~1.96) 0.133
AST (U/L) 67(6-557) 92.1(16-1680) 0.614
ALT (U/L) 105.7(6-1287) 83.4(6-2285) 0.748
Total bilirubin
(mg/dL) 1.01(0.42-2.54) 0.98(0.28-2.68) 0.841 4.10 OATP1B1*5
5
5.1
97 59 (60.8%) 16
(16.5%) 43 (44.3%)
( AST<30 U/L ALT<35 U/L )
( 54 86) ( 5.1)
5.1
*
(%)
Chen (2007) 97 Hepatotoxitity (CIOMS definition) 59 60.8
Chen (2007) 97 Liver Injury (CIOMS definition) 16 16.5
Kao (2006) 254 Hepatotoxitity (CIOMS definition) 126 49.61
Kao (2006) 254 Liver Injury (CIOMS definition) 52 20.47
Lo (1998) 348 Hepatotoxitity (CIOMS definition) 207 59.48
Lo (1998) 348 Liver Injury (CIOMS definition) 120 34.50
Chen (2002) 261 Hepatotoxitity (CIOMS definition) 152 58.24
Chen (2002) 261 Liver Injury (CIOMS definition) 83 31.80
Hsiao (2003) 245 Hepatotoxicity (CIOMS definition) 122 49.80
Hsiao (2003) 245 Liver Injury (CIOMS definition) 41 16.73
OATP1B1 allele frquency
OATP1B1
OATP1B1*1b OATP1B1*5 OATP1B1*15 OATP1B1*1a allele
OATP1B1*1b(64.9%) OATP1B1*1a (24.2%) wild type
OATP1B1 OATP1B1*1b OATP1B1*1a OATP1B1
wild type ( 5.2 5.3)
*1a 24.2% 22.22% 35.2%
80% 30% 75%
Chen (N=97) Lu (N=162) Japanese (N=267) OATP1B1 genotype
5.3 OATP1B1 allele frequency
OATP1B1 allele frequency
OATP1B1 allele frequency
1. OATP1B1
2. OATP1B1
3. OATP1B1
( )
( NAT2 CYP2E1 )
5.2
1.
16 OATP1B1
primary outcome =0.05
power=0.8 20%
38 190 allele
OATP1B1*5 primary outcome =0.05 power=0.8 20%
2797 13985 ( Power and Sample
Size Calculations Ver2.1.31 )
2.
Tbil Dbil ALP
3.
OATP1B1 rifampin
rifampin isoniazid pyrazinamide
4. OATP1B1 rifampin
OATP1B1 rifampin
(in vitro) (in vivo)
OATP1B1 rifampin
5. OATP1B1
OATP1B1*1a OATP1B1*1b OATP1B1*5 OATP1B1*15 OATP1B1
5
rifampin
OATP1B1
6
4
1. 16.5%
2. OATP1B1*1b(64.9%) OATP1B1*1a (24.2%) allele frequency
3. OATP1B1*1a/*5
4. OATP1B1*1b OATP1B1*5 OATP1B1*15
OATP1B1 4
1. . . : ; 2004.
2. Charles A. Peloquin. Chapter 110: Tuberculosis. In: Joseph T. Dipiro, Robert L.
Talbert, Gary C.Yee, Gary R. Matzke, Barbara G. Wells, L. Michael Posey, eds.
Pharmacotherapy: A pathopnysiologic approach 6ed: Mc Graw-Hill Publishing Co. ; 2005:2015-34.
3. 2006 Tuberculosis Facts. 2007. (Accessed March, 2007, at
http://www.who.int/tb/publications/2006/tb_factsheet_2006_1_en.pdf.)
4. . (Accessed 20 March, 2007, at
http://www.doh.gov.tw/statistic/data/ 2/94/ / .htm.) 5. . 2006. (Accessed 23 August, 2006, at
http://203.65.72.83/ch/dt/upload/QC/epi/epi_face.htm.)
9. Neff M, Ats, Cdc, Idsa. ATS, CDC, and IDSA update recommendations on the treatment of tuberculosis. Am Fam Physician 2003;68(9):1854-62.
10. Blumberg HM, Leonard MK, Jasmer RM. Update on the Treatment of Tuberculosis and Latent Tuberculosis Infection. JAMA 2005;293(22):2776-84.
11. . - . ; 2006.
12. Holt CD, Arriola E. Chapter 30: Adverse Effects of Drugs on rhe liver. In:
Koda-Kimble MA, Young LY, Kradjan WA, Guglielmo BJ, Alldredge BA, Corelli RL, eds. Applied Therapeutics: The Clinical Use of Drugs 8 ed: Lippincott Williams & Wilkins; 2004:1-25.
13. Victor J. Navarro, John R.Senior. Drug-related Hepatotoxicity. The New England Journal of Medicine 2006;354(7):731-9.
14. Friis H, Andreasen PB. Drug-induced hepatic injury: an analysis of 1100 cases reported to the Danish Committee on Adverse Drug Reactions between 1978 and 1987. Journal of Internal Medicine 1992;232(2):133-8.
15. Chitturi S FG. Drug-induced liver disease. In: Schiff ER SM, Maddrey WC, ed.
Schiff’s diseases of the liver, 9th ed. Philadelphia: Lippincott, Williams & Wilkins;
2002:1059–128.
16. Larrey D. Epidemiology and individual susceptibility to adverse drug reactions affecting the liver. Semin Liver Dis 2002;22(2):145-55.
17. Jussi J. Saukkonen DLC, Robert M. Jasmer, Steven Schenker, John A. Jereb,. An Official ATS Statement: Hepatotoxicity of Antituberculosis Therapy. Am J Respir
18. Ostapowicz GM FR, Schiødt F, Larson A, Davern T, Steven Han H, McCashland T, Shakil A, Hay J, Hynan L, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002;137:947~54.
19. William M. Lee. Drug-Induced Hepatotoxicity. The New England Journal of Medicine 2003;349(5):474-85.
20. B. Kevin Park, Neil R. Kitteringham, James L. Maggs. The Role of Metabolic Activation in Drug-Induced Hepatotoxicity. Annu Rev Pharmacol Toxicol 2005;45:177-202.
21. Benichou C. Criteria of Drug-Induced Liver Disorders. Report of an international consensus meeting. Journal of Hepatology 1990;11(2):272-6.
22. Yew WW, Leung CC. Antituberculosis drugs and hepatotoxicity. Respirology 2006;11:699-707.
23. RM. W. Fatal hepatotoxicity of antitubercular chemotherapy. Lancet 1991;338:
1083~4.
24. Tost JR VR, Cayla J, Diaz-Cabanela D, Jimenez A, Broquetas JM. Study Group of Severe Hepatotoxicity due to Anti-tuberculosis Drugs. Severe hepatotoxicity due to anti-tuberculosis drugs in Spain. Int J Tuberc Lung Dis 2005;9:534~40.
25. Sharifzadeh M, Rasoulinejad M, Valipour F, Nouraie M, Vaziri S. Evaluation of patient-related factors associated with causality, preventability, predictability and severity of hepatotoxicity during antituberculosis treatment. Pharmacol Res 2005;51(4):353-8.
26. Shakya R RB, Shrestha B. Incidence of hepatotoxicity due to antitubercular medicines and assessment of risk factors. Ann Pharmacother 2004;38:1074~9.
27. Nolan CM. Isoniazid for latent tuberculosis infection. Approaching 40 and reaching its prime. Am J Respir Crit Care Med 2003;168:412~3.
28. Steele MA, Burk, R.F., DesPrez, R.M. Toxic hepatitis with isoniazid and rifampicin.
A meta-analysis. Chest 1991;99:465~71.
29. Jasmer RM, Daley, C.L. Rifampicin and pyrazinamide for treatment of latent tuberculosis infection: is it safe. Am J Respir Crit Care Med 2003;167:809~10.
30. CDC/ATS. Update: adverse event data and revised American Thoracic Society/CDC recommendations against the use of rifampicin and pyrazinamide for treatment of latent tuberculosis infection in United States. MMWR Morb Mortal Wkly Rep 2003;52:735~9.
31. Sharma SK. Antituberculosis drugs and hepatotoxicity. Infection, Genetics and Evolution 2004;4:167~70.
32. Sodhi CP, Rana, S.V., Mehta, S.K., Vaiphei, K., Attari, S., Mehta, S. Study of oxidative-stress in isoniazid-rifampicin induced hepatic injury in young rats. Drug Chem Toxicol 1997;20:255~69.
33. Huang YS CH, Su WJ, Wu JC, Lai SL, Yang SY, Chang FY, Lee SD. Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis. Hepatology 2002;35:883~9.
34. Huang YS CH, Su WJ, Wu JC, Chang SC, Chiang CH, Chang FY, Lee SD.
36. Mitchell JR TU, Black M, Timbrell JA, Snodgrass WR,Potter WZ, Jollow HR, Keiser HR. 1975. Clin Pharmacol Ther Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydrazine metabolites.;18:70~9.
37. Attri S RS, Vaiphie K, Katyal R, Sodhi CP, Kanwar S, Singh K. Protective effect of N-acetylcysteine in isoniazid induced hepatic injury in growing rats. Indian J Exp Biol 2001;39:436~40.
38. Sodhi CP RS, Mehta SK, Vaiphei K, Attri S, Thakur S, Mehta S. Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without
protein-energy malnutrition. J Biochem Toxicol 1996;11:139~46.
39. Farrell GC. Drug-induced acute hepatitis. In: Farrell GC, ed. Drug-induced liver disease. New York Churchill Livingstone; 1994.
40. Smith CA WM, Gough AC, Harrison DJ, Wolf CR, Rane A. A simplified assay for the arylamine N-acetyltransferase 2 polymorphism validated by phenotyping with isoniazid. J Med Genet 1997;34:758~60.
41. Reith K KA, Toren P, et al. Disposition and metabolism of 14C-rifapentine in healthy volunteers. Drug Metab Dispos 1998;26:732-8.
42. Davies DM. In: D.M. Davies REF, H. de Glanville., ed. Davies's textbook of adverse drug reactions. London New York Chapman & Hall Medical 1998:292.
43. Zimmerman HJ. Hepatic injury from antimicrobial agents. In: Hepatotoxicity : the adverse effects of drugs and other chemicals on the liver Philadelphia Lippincott Williams & Wilkins; 1999:589~637.
44. Huang C-S. Molecular genetics of unconjugated hyperbilirubinemia in Taiwanese.
Journal of Biomedical Science 2005;12:445-50.
45. Mikko Niemi KTK, Ute Hofmann, Matthias Schwab, Michel Eichelbaum, Martin F.
Fromm, 1. Fexofenadine pharmacokinetics are associated with a polymorphism of the SLCO1B1 gene (encoding OATP1B1). Br J Clin Pharmacol 2005;59(5):602-4.
46. Thompson NP, Caplin ME, Hamilton MI, et al. Anti-tuberculosis medication and the liver: dangers and recommendations in management. Eur Respir J 1995;8(8):1384-8.
47. Park BK, Kitteringham NR, Maggs JL, Pirmohamed M, Williams DP. The role of metabolic activation in drug-induced hepatotoxicity. Annu Rev Pharmacol Toxicol 2005;45:177-202.
48. Sharma SK, Balamurugan A, Saha PK, Pandey RM, Mehra NK. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. Am J Respir Crit Care Med 2002;166(7):916-9.
49. Hwang SJ WJ, Lee CN, Yen FS, Lu CL, Lin TP, Lee SD. A prospective clinical study of isoniazid-rifampin-pyrazinamide-induced liver injury in an area endemic for hepatitis B. Journal of gastroenterology and hepatology 1997;12:87~91.
50. Dufour DR LJ, Nolte FS, Gretch DR, Koff RS, Seeff LB. Diagnosis and monitoring of hepatic injury: I. Performance characteristics of laboratory tests. Clin Chem 2000;46:2027~49.
51. Huang Y-S, Chern H-D, Su W-J, et al. Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis.
Hepatology 2002;35(4):883-9.
52. . . :
; 1999.
55. Singh J AA, Garg PK, Thalur VS, Pande JN, Tandon RK. Antituberculosis treatment-induced hepatotoxicity: role of predictive factors. Postgrad Med J 1995;71:359~62.
56. Pande JN SS, Khilnani GC, Khilnani S, Tandon RK. Risk factors for hepatotoxicity from antituberculosis drugs: a case-control study. Thorax 1996;51:132~6.
57. Durand F JG, Pessayre D, Fournier M, Bernuau J. Hepatotoxicity of antitubercular treatments: rationale for monitoring liver status. Drug Saf 1996;15:394~405.
58. Wu JC LS, Yeh PF, Chan C, Wang Y, Huang Y, Tsai Y, Lee P, Ting L, Lo K.
Isoniazid-rifampin-induced hepatitis in hepatitis B carriers. Gastroenterology 1990;98:502~4.
59. Fernandez-Villar A, Sopena B, Vazquez R, et al. Isoniazid hepatotoxicity among drug users: the role of hepatitis C. Clin Infect Dis 2003;36(3):293-8.
60. Fernandez-Villar A, Sopena B, Fernandez-Villar J, et al. The influence of risk factors on the severity of anti-tuberculosis drug-induced hepatotoxicity. Int J Tuberc Lung Dis 2004;8(12):1499-505.
61. Ungo JR JD, Ashkin D, Hollender E, Bernstein D, Albanese A, Pitchenik A.
Antituberculosis drug-induced hepatotoxicity: the role of hepatitis C virus and the human immunodeficiency virus. Am J Respir Crit Care Med 1998;157:1871~6.
62. . . : ;
2006.
63. Rommel G. Tirona RBK. Pharmacogenomics of organic anion-transporting polypeptides (OATP). Advanced Drug Delivery Reviews 2002;54:1343–52.
64. B. Hagenbuch PJM. The superfamily of organic anion transporting polypeptides.
Biochimica et Biophysica Acta 2003;1609:1~18.
65. Tsuyoshi MIKKAICHI TS, Masayuki TANEMOTO, Sadayoshi ITO1, Takaaki ABE.
The Organic Anion Transporter (OATP) Family. Drug Metab Pharmacokin 2004;19(3):171-9.
66. Meier BHPJ. Organic anion transporting polypeptides of the OATP/SLC21
family:phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers Arch - Eur J Physiol 2004;447:653-65.
67. Pubmed-Entrez Gene. (Accessed 15 May, 2007, at
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=gene.)
68. DRUG-DRUG INTERACTIONS IN VIVO AND IN VITRO STUDIES: Focus on Transporters. 2004. (Accessed at
www.fda.gov/ohrms/dockets/ac/04/slides/2004-4079S1_09_Giacomini.ppt) 69. DuBuske LM. The Role of P-Glycoprotein and Organic Anion-Transporting
Polypeptides in Drug Interactions. Drug Safety 2005;28(9):789-801.
70. Catia Marzolini RGT, Richard B Kim. Pharmacogenomics of the OATP and OAT families. Pharmacogenomics 2004;5(3):273-82.
71. Kim RB. 3-Hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors (statins) and genetic variability (single nucleotide polymorphisms) in a hepatic drug uptake transporter: What’s it all about? CLINICAL PHARMACOLOGY &
73. Nozawa T NM, Tamai I, Noda K, Nezu J, Sai Y, Tsuji A, Yokoi T. Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis. J Pharmacol Exp Ther 2002;302:804-13.
74. Iwai M SH, Ieiri I, Otsubo K, Sugiyama Y. Functional analysis of single nucleotide polymorphisms of hepatic organic anion transporter OATP1B1 (OATP-C).
Pharmacogenetics 2004;14:749-57.
75. Nozawa T MH, Sugiura S, Tsuji A, Tamai I Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms. Drug Metab Dispos 2005;33(3):434-9.
76. Ichiro Ieiria, Hiroshi Suzukib, Miyuki Kimurac, Hiroshi Takanea, Yohei Nishizatod, Shin Iriec, Akinori Uraec, Kiyoshi Kawabatae, Shun Higuchid, Kenji Otsuboa, Yuichi Sugiyamab. Influence of common variants in the pharmacokinetic genes (OATP-C, UGT1A1, and MRP2) on serum bilirubin levels in healthy subjects.
Hepatology Research 2004;30:91-5.
77. Huang CS HM, Lin MS, Yang SS, Teng HC, Tang KS. Genetic factors related to unconjugated hyperbilirubinemia amongst adults. Pharmacogenet Genomics 2005;15:43-50.
78. Marja K. Pasanen JTB, Pertti J. Neuvonen , Mikko Niemi. Frequencies of single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide 1B1 SLCO1B1 gene in a Finnish population. Eur J Clin Pharmacol 2006;62:409-15.
79. Fromm JKASUGMF. Pharmacogenomics of human OATP transporters. Naunyn Schmied Arch Pharmacol 2006;372(6):432-43.
80. Mwinyi J JA, Bauer S, Roots I, Gerloff T. Evidence for inverse effects of OATP-C (SLC21A6) *5 and *1b haplotypes on pravastatin kinetics. Clin Pharmacol Ther 2004;75(5):381-5.
81. Wei Zhang Y-JH, Chun-Ting Han, Zhao-Qian Liu. Effect of SLCO1B1 genetic polymorphism on the pharmacokinetics of nateglinide. Br J Clin Pharmacol 2006;62(5):567–72.
82. ROMMEL G. TIRONA BFL, ALLAN W. WOLKOFF, and RICHARD B. KIM.
Human Organic Anion Transporting Polypeptide-C (SLC21A6) Is a Major Determinant of Rifampin-Mediated Pregnane X Receptor Activation. THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2003;304:223-8.
83. S. Gentile MP, G. Baldini, G. Lunazzi, C. Tiribelli, G.L. Sottocasa,. The implication of bilitranslocase function in the impaired rifamycin SV metabolism in Gilbert's syndrome,. Clin Sci 1985;68:675-80.
84. S. Gentile RM, M. Persico, P. Bronzino, M. Coltorti,. Impaired plasma clearance of nicotinic acid and rifamycin-SV in Gilbert’s syndrome: evidence of a functional heterogeneity. Hepato-Gastroenterology 1985;32:113-6.
85. G. Acocella FBN, L.T. Tenconi. The effect of an intravenous infusion of rifamycin SV on the excretion of bilirubin, bromsulphalein, and indocyanine green in man.
Gastroenterology 1965;49:521-5.
86. . . :