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result sql = Pharmacokinetics and tissue distribution of betulinic acid in CD-1 mice.
Pharmacokinetics and tissue distribution of betulinic acid in CD-1 mice.
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char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = H;code = 72
char = P;code = 80
char = L;code = 76
char = C;code = 67
char = /;code = 47
char = M;code = 77
char = S;code = 83
char = .;code = 46
char = ;code = 32
char = O;code = 79
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = d;code = 100
char = e;code = 101
char = c;code = 99
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = P;code = 80
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = r;code = 114
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 = c;code = 99
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = W;code = 87
char = i;code = 105
char = n;code = 110
char = N;code = 78
char = o;code = 111
char = n;code = 110
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = f;code = 102
char = t;code = 116
char = w;code = 119
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = c;code = 99
char = k;code = 107
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = o;code = 111
char = -;code = 45
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = r;code = 114
char = s;code = 115
char = t;code = 116
char = -;code = 45
char = o;code = 111
char = r;code = 114
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = I;code = 73
char = P;code = 80
char = ;code = 32
char = 2;code = 50
char = 5;code = 53
char = 0;code = 48
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 5;code = 53
char = 0;code = 48
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = a;code = 97
char = k;code = 107
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 1;code = 49
char = 5;code = 53
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 2;code = 50
char = 3;code = 51
char = ;code = 32
char = h;code = 104
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = 2;code = 50
char = 5;code = 53
char = 0;code = 48
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 5;code = 53
char = 0;code = 48
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = I;code = 73
char = P;code = 80
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
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 = f;code = 102
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = h;code = 104
char = a;code = 97
char = l;code = 108
char = f;code = 102
char = -;code = 45
char = l;code = 108
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 1;code = 49
char = 1;code = 49
char = .;code = 46
char = 5;code = 53
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = 1;code = 49
char = 1;code = 49
char = .;code = 46
char = 8;code = 56
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char = h;code = 104
char = ;code = 32
char = a;code = 97
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char = ;code = 32
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
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char = e;code = 101
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 1;code = 49
char = 3;code = 51
char = .;code = 46
char = 6;code = 54
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = 1;code = 49
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char = .;code = 46
char = 5;code = 53
char = ;code = 32
char = L;code = 76
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = /;code = 47
char = h;code = 104
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = m;code = 109
char = a;code = 97
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char = o;code = 111
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = e;code = 101
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char = s;code = 115
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = I;code = 73
char = P;code = 80
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
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char = 5;code = 53
char = 0;code = 48
char = 0;code = 48
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char = g;code = 103
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char = k;code = 107
char = g;code = 103
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char = i;code = 105
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = s;code = 115
char = k;code = 107
char = i;code = 105
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char = o;code = 111
char = f;code = 102
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char = l;code = 108
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char = ;code = 32
char = (;code = 40
char = h;code = 104
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char = 1;code = 49
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char = );code = 41
char = ;code = 32
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char = 7;code = 55
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char = (;code = 40
char = h;code = 104
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char = -;code = 45
char = 1;code = 49
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char = );code = 41
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 2;code = 50
char = 3;code = 51
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char = ,;code = 44
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char = t;code = 116
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char = 1;code = 49
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char = a;code = 97
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char = p;code = 112
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char = a;code = 97
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char = );code = 41
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char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
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char = );code = 41
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char = (;code = 40
char = h;code = 104
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char = ;code = 32
char = 2;code = 50
char = 0;code = 48
char = .;code = 46
char = 2;code = 50
char = ,;code = 44
char = ;code = 32
char = V;code = 86
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char = (;code = 40
char = L;code = 76
char = /;code = 47
char = k;code = 107
char = g;code = 103
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char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 6;code = 54
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = A;code = 65
char = U;code = 85
char = C;code = 67
char = ;code = 32
char = (;code = 40
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = /;code = 47
char = h;code = 104
char = /;code = 47
char = m;code = 109
char = L;code = 76
char = );code = 41
char = ;code = 32
char = 3;code = 51
char = 5;code = 53
char = 0;code = 48
char = 4;code = 52
char = ,;code = 44
char = ;code = 32
char = T;code = 84
char = (;code = 40
char = m;code = 109
char = a;code = 97
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char = );code = 41
char = ;code = 32
char = (;code = 40
char = h;code = 104
char = );code = 41
char = ;code = 32
char = 3;code = 51
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char = 9;code = 57
char = 0;code = 48
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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char = C;code = 67
char = (;code = 40
char = m;code = 109
char = a;code = 97
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char = );code = 41
char = ;code = 32
char = (;code = 40
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = /;code = 47
char = m;code = 109
char = L;code = 76
char = );code = 41
char = ;code = 32
char = 3;code = 51
char = 0;code = 48
char = 0;code = 48
char = .;code = 46
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char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
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char = t;code = 116
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = c;code = 99
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char = d;code = 100
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char = i;code = 105
char = n;code = 110
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char = t;code = 116
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = u;code = 117
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 2;code = 50
char = 4;code = 52
char = ;code = 32
char = h;code = 104
char = ;code = 32
char = p;code = 112
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char = d;code = 100
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char = ;code = 32
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char = s;code = 115
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char = i;code = 105
char = r;code = 114
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char = l;code = 108
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char = ;code = 32
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char = ;code = 32
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char = l;code = 108
char = ;code = 32
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char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ,;code = 44
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char = a;code = 97
char = e;code = 101
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char = m;code = 109
char = ,;code = 44
char = ;code = 32
char = l;code = 108
char = u;code = 117
char = n;code = 110
char = g;code = 103
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = m;code = 109
char = u;code = 117
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = k;code = 107
char = i;code = 105
char = d;code = 100
char = n;code = 110
char = e;code = 101
char = y;code = 121
char = ,;code = 44
char = ;code = 32
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char = k;code = 107
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = r;code = 114
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result sql = Betulinic acid is a naturally occurring pentacyclic triterpenoid. Betulinic acid has recently been selected by the National Cancer Institute for addition into the RAID (Rapid Access to Intervention in Development) programme. The agent exhibits potential anti-tumour activity and functions in this regard via apoptosis. The objective of the present study was to determine the pharmacokinetics of betulinic acid in CD-1 mice. Serum samples were obtained at designed times after a single 250 or 500 mg/kg intraperitoneal (IP) dose of betulinic acid. Tissue samples (skin, heart, liver, spleen, kidney, lung, brain, colon, caecum, ovary, uterus, thymus, lymph node, bladder, perirenal fat, mammary gland and small intestine) were collected after betulinic acid administration (500 mg/kg). Betulinic acid was extracted with methylene chloride and quantitatively analysed by HPLC/MS. Oleanolic acid and madecassic acid were used as internal standards. Pharmacokinetic parameters were calculated using the WinNonlin pharmacokinetic software package. A two-compartment, first-order model was selected for pharmacokinetic modelling. The results showed that after IP 250 and 500 mg/kg betulinic acid, the serum concentrations reached peaks at 0.15 and 0.23 h, respectively. The 250 and 500 mg/kg above betulinic acid IP doses were found to have elimination half-lives of 11.5 and 11.8 h and total clearances of 13.6 and 13.5 L/kg/h, respectively. The pharmacokinetic parameters observed for IP betulinic acid 500 mg/kg in the skin of mice were as follows: k(a) (h(-1)) 0.257, k(10) (h(-1)) 0.234, t(1/2(alpha)) (h) 2.63, t(1/2(beta)) (h) 20.2, V (L/kg) 0.61, AUC (microg/h/mL) 3504, T(max) (h) 3.90 and C(max) (microg/mL) 300.9. The distribution of betulinic acid in tissues at 24 h post-IP administration in a descending order was as follows: perirenal fat, ovary, spleen, mammary gland, uterus, bladder, lymph node, liver, small intestine, caecum, lung, thymus, colon, kidney, skin, heart and brain.

Publication: Biopharm Drug Dispos 1999 Nov ;20(8)::379-83.
Publication Date: 1999 Nov
Study Author(s): Udeani, G O;Zhao, G M;Geun Shin, Y;Cooke, B P;Graham, J;Beecher, C W;Kinghorn, A D;Pezzuto, J M;
Institution: Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA. [email protected]
Shortcut link to this study:
Betulinic acid is a naturally occurring pentacyclic triterpenoid. Betulinic acid has recently been selected by the National Cancer Institute for addition into the RAID (Rapid Access to Intervention in Development) programme. The agent exhibits potential anti-tumour activity and functions in this regard via apoptosis. The objective of the present study was to determine the pharmacokinetics of betulinic acid in CD-1 mice. Serum samples were obtained at designed times after a single 250 or 500 mg/kg intraperitoneal (IP) dose of betulinic acid. Tissue samples (skin, heart, liver, spleen, kidney, lung, brain, colon, caecum, ovary, uterus, thymus, lymph node, bladder, perirenal fat, mammary gland and small intestine) were collected after betulinic acid administration (500 mg/kg). Betulinic acid was extracted with methylene chloride and quantitatively analysed by HPLC/MS. Oleanolic acid and madecassic acid were used as internal standards. Pharmacokinetic parameters were calculated using the WinNonlin pharmacokinetic software package. A two-compartment, first-order model was selected for pharmacokinetic modelling. The results showed that after IP 250 and 500 mg/kg betulinic acid, the serum concentrations reached peaks at 0.15 and 0.23 h, respectively. The 250 and 500 mg/kg above betulinic acid IP doses were found to have elimination half-lives of 11.5 and 11.8 h and total clearances of 13.6 and 13.5 L/kg/h, respectively. The pharmacokinetic parameters observed for IP betulinic acid 500 mg/kg in the skin of mice were as follows: k(a) (h(-1)) 0.257, k(10) (h(-1)) 0.234, t(1/2(alpha)) (h) 2.63, t(1/2(beta)) (h) 20.2, V (L/kg) 0.61, AUC (microg/h/mL) 3504, T(max) (h) 3.90 and C(max) (microg/mL) 300.9. The distribution of betulinic acid in tissues at 24 h post-IP administration in a descending order was as follows: perirenal fat, ovary, spleen, mammary gland, uterus, bladder, lymph node, liver, small intestine, caecum, lung, thymus, colon, kidney, skin, heart and brain.
PMID: 10870094

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