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char = d;code = 100
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char = c;code = 99
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char = n;code = 110
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char = 5;code = 53
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char = ;code = 32
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char = e;code = 101
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char = r;code = 114
char = a;code = 97
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char = l;code = 108
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char = f;code = 102
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char = I;code = 73
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char = ;code = 32
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char = P;code = 80
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char = R;code = 82
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char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = d;code = 100
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char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
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char = a;code = 97
char = l;code = 108
char = ;code = 32
char = p;code = 112
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char = v;code = 118
char = a;code = 97
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = -;code = 45
char = S;code = 83
char = a;code = 97
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = A;code = 65
char = f;code = 102
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = .;code = 46
result sql = Nuclear receptor-mediated induction of CYP450 by antiretrovirals: functional consequences of NR1I2 (PXR) polymorphisms and differential prevalence in whites and sub-Saharan Africans.
Nuclear receptor-mediated induction of CYP450 by antiretrovirals: functional consequences of NR1I2 (PXR) polymorphisms and differential prevalence in whites and sub-Saharan Africans.
char = <;code = 60
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char = >;code = 62
char = B;code = 66
char = A;code = 65
char = C;code = 67
char = K;code = 75
char = G;code = 71
char = R;code = 82
char = O;code = 79
char = U;code = 85
char = N;code = 78
char = D;code = 68
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
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char = b;code = 98
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char = A;code = 65
char = n;code = 110
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char = i;code = 105
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = r;code = 114
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char = i;code = 105
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char = l;code = 108
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char = t;code = 116
char = h;code = 104
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char = a;code = 97
char = p;code = 112
char = y;code = 121
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char = c;code = 99
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char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = H;code = 72
char = I;code = 73
char = V;code = 86
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char = p;code = 112
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char = c;code = 99
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char = p;code = 112
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char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
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char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = s;code = 115
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char = f;code = 102
char = ;code = 32
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char = m;code = 109
char = e;code = 101
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char = P;code = 80
char = 4;code = 52
char = 5;code = 53
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char = a;code = 97
char = c;code = 99
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char = ;code = 32
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char = <;code = 60
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char = <;code = 60
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char = H;code = 72
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char = 3;code = 51
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char = N;code = 78
char = R;code = 82
char = 1;code = 49
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char = 2;code = 50
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char = (;code = 40
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char = g;code = 103
char = ;code = 32
char = P;code = 80
char = X;code = 88
char = R;code = 82
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = S;code = 83
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = o;code = 111
char = ;code = 32
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = D;code = 68
char = a;code = 97
char = r;code = 114
char = u;code = 117
char = n;code = 110
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = m;code = 109
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = p;code = 112
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = l;code = 108
char = f;code = 102
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = a;code = 97
char = c;code = 99
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = Y;code = 89
char = P;code = 80
char = 3;code = 51
char = A;code = 65
char = 4;code = 52
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = /;code = 47
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = C;code = 67
char = Y;code = 89
char = P;code = 80
char = 2;code = 50
char = B;code = 66
char = 6;code = 54
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = P;code = 80
char = X;code = 88
char = R;code = 82
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = -;code = 45
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = Y;code = 89
char = P;code = 80
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = P;code = 80
char = X;code = 88
char = R;code = 82
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = y;code = 121
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = m;code = 109
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = -;code = 45
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = p;code = 112
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = Y;code = 89
char = P;code = 80
char = 3;code = 51
char = A;code = 65
char = 4;code = 52
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = P;code = 80
char = X;code = 88
char = R;code = 82
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = l;code = 108
char = f;code = 102
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = N;code = 78
char = R;code = 82
char = 1;code = 49
char = I;code = 73
char = 2;code = 50
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = Y;code = 89
char = P;code = 80
char = 3;code = 51
char = A;code = 65
char = 4;code = 52
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = Y;code = 89
char = P;code = 80
char = 2;code = 50
char = B;code = 66
char = 6;code = 54
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = v;code = 118
char = i;code = 105
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = -;code = 45
char = S;code = 83
char = a;code = 97
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = A;code = 65
char = f;code = 102
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = .;code = 46
result sql = BACKGROUND : Antiretroviral therapy including HIV protease inhibitors and nonnucleoside reverse transcriptase inhibitors can both inhibit and induce expression of cytochrome P450s, potentially leading to drug interactions. However, information is lacking on the impact of genetic polymorphism on this interaction.

METHODS : This study examines the prevalence of 33 polymorphisms in NR1I2 (pregnane X receptor [PXR]), CYP3A4, and CYP2B6 in 1013 white and sub-Saharan African patients with HIV; explores the inductive ability of 16 antiretrovirals on CYP3A4 and CYP2B6 promoter activity through nuclear receptors PXR and constitutive androstane receptor (CAR); and evaluates the influence of naturally occurring PXR genetic variants on antiretroviral activation.

RESULTS : Seventeen polymorphisms were present at different frequencies between the two ethnicities. Darunavir, fosamprenavir, lopinavir, nelfinavir, tipranavir, efavirenz, and abacavir increased CYP3A4 and/or CYP2B6 promoter activity, some through constitutive androstane receptor but mainly through PXR. Addition of low-dose ritonavir enhanced levels of CYP promoter activity for several protease inhibitors. Some PXR variants displayed lower fosamprenavir- and lopinavir-induced CYP3A4 promoter activity than the PXR reference sequence, whereas efavirenz and nelfinavir induction was unchanged.

CONCLUSIONS : The presence of NR1I2 polymorphisms can alter the induction of CYP3A4 and CYP2B6 promoter activity, potentially adding to the unpredictable nature of antiretroviral drug interactions. These polymorphisms differ in prevalence between whites and sub-Saharan Africans.

Publication: J. Acquir. Immune Defic. Syndr. 2010 Dec 15 ;55(5)::536-49. :doi: 10.1097/QAI.0b013e3181f52f0c.
Publication Date: 2010 Dec 15
Study Author(s): Svärd, Jenny;Spiers, J Paul;Mulcahy, Fiona;Hennessy, Martina;
Institution: Department of Pharmacology & Therapeutics, Trinity College, Dublin, Ireland.
Shortcut link to this study:
BACKGROUND : Antiretroviral therapy including HIV protease inhibitors and nonnucleoside reverse transcriptase inhibitors can both inhibit and induce expression of cytochrome P450s, potentially leading to drug interactions. However, information is lacking on the impact of genetic polymorphism on this interaction.

METHODS : This study examines the prevalence of 33 polymorphisms in NR1I2 (pregnane X receptor [PXR]), CYP3A4, and CYP2B6 in 1013 white and sub-Saharan African patients with HIV; explores the inductive ability of 16 antiretrovirals on CYP3A4 and CYP2B6 promoter activity through nuclear receptors PXR and constitutive androstane receptor (CAR); and evaluates the influence of naturally occurring PXR genetic variants on antiretroviral activation.

RESULTS : Seventeen polymorphisms were present at different frequencies between the two ethnicities. Darunavir, fosamprenavir, lopinavir, nelfinavir, tipranavir, efavirenz, and abacavir increased CYP3A4 and/or CYP2B6 promoter activity, some through constitutive androstane receptor but mainly through PXR. Addition of low-dose ritonavir enhanced levels of CYP promoter activity for several protease inhibitors. Some PXR variants displayed lower fosamprenavir- and lopinavir-induced CYP3A4 promoter activity than the PXR reference sequence, whereas efavirenz and nelfinavir induction was unchanged.

CONCLUSIONS : The presence of NR1I2 polymorphisms can alter the induction of CYP3A4 and CYP2B6 promoter activity, potentially adding to the unpredictable nature of antiretroviral drug interactions. These polymorphisms differ in prevalence between whites and sub-Saharan Africans.
PMID: 20861742

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