|
|
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result sql = Pharmacokinetic interactions of cyclosporine with etoposide and mitoxantrone in children with acute myeloid leukemia.
Pharmacokinetic interactions of cyclosporine with etoposide and mitoxantrone in children with acute myeloid leukemia.char = T;code = 84
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char = t;code = 116
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char = e;code = 101
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result sql = The purpose of this study was to assess the effect of the multidrug resistance modulator cyclosporine (CsA) on the pharmacokinetics of etoposide and mitoxantrone in children with de novo acute myeloid leukemia (AML). Serial blood samples for pharmacokinetic studies were obtained in 38 children over a 24-h period following cytotoxin treatment with or without CsA on days 1 and 4. Drug concentrations were quantitated using validated HPLC methods, and pharmacokinetic parameters were determined using compartmental modeling with an iterative two-stage approach, implemented on ADAPT II software. Etoposide displayed a greater degree of interindividual variability in clearance and systemic exposure than mitoxantrone. With CsA treatment, etoposide and mitoxantrone mean clearance declined by 71% and 42%, respectively. These effects on clearance, in combination with the empiric 40% dose reduction for either cytotoxin, resulted in a 47% and 12% increases in the mean AUC for etoposide and mitoxantrone, respectively. There were no differences in the rates of stomatitis or infection between the two groups. CsA treatment resulted in an increased incidence of hyperbilrubinemia, which rapidly reversed upon conclusion of drug therapy. The variability observed in clearance, combined with the empiric 40% dose reduction of the cytotoxins, resulted in statistically similar systemic exposure and similar toxicity.
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char = o;code = 111
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result sql = Pharmacokinetic interactions of cyclosporine with etoposide and mitoxantrone in children with acute myeloid leukemia.
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char = r;code = 114
char = o;code = 111
char = n;code = 110
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
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char = i;code = 105
char = l;code = 108
char = d;code = 100
char = r;code = 114
char = e;code = 101
char = n;code = 110
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = e;code = 101
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char = n;code = 110
char = o;code = 111
char = v;code = 118
char = o;code = 111
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char = a;code = 97
char = c;code = 99
char = u;code = 117
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = y;code = 121
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = u;code = 117
char = k;code = 107
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = a;code = 97
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char = (;code = 40
char = A;code = 65
char = M;code = 77
char = L;code = 76
char = );code = 41
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = o;code = 111
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = a;code = 97
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = s;code = 115
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 = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = i;code = 105
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
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char = o;code = 111
char = b;code = 98
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 3;code = 51
char = 8;code = 56
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = d;code = 100
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = 2;code = 50
char = 4;code = 52
char = -;code = 45
char = h;code = 104
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = C;code = 67
char = s;code = 115
char = A;code = 65
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = y;code = 121
char = s;code = 115
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 4;code = 52
char = .;code = 46
char = ;code = 32
char = D;code = 68
char = r;code = 114
char = u;code = 117
char = g;code = 103
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 = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = q;code = 113
char = u;code = 117
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = t;code = 116
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 = v;code = 118
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = H;code = 72
char = P;code = 80
char = L;code = 76
char = C;code = 67
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = o;code = 111
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = p;code = 112
char = h;code = 104
char = a;code = 97
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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
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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
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char = r;code = 114
char = s;code = 115
char = ;code = 32
char = w;code = 119
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char = r;code = 114
char = e;code = 101
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char = d;code = 100
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = r;code = 114
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char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = s;code = 115
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char = n;code = 110
char = g;code = 103
char = ;code = 32
char = c;code = 99
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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 = a;code = 97
char = l;code = 108
char = ;code = 32
char = m;code = 109
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char = d;code = 100
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
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char = i;code = 105
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = t;code = 116
char = w;code = 119
char = o;code = 111
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char = s;code = 115
char = t;code = 116
char = a;code = 97
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char = e;code = 101
char = ;code = 32
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char = p;code = 112
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char = a;code = 97
char = c;code = 99
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char = p;code = 112
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char = e;code = 101
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char = ;code = 32
char = A;code = 65
char = D;code = 68
char = A;code = 65
char = P;code = 80
char = T;code = 84
char = ;code = 32
char = I;code = 73
char = I;code = 73
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
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char = .;code = 46
char = ;code = 32
char = E;code = 69
char = t;code = 116
char = o;code = 111
char = p;code = 112
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char = e;code = 101
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char = d;code = 100
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char = s;code = 115
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char = a;code = 97
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char = d;code = 100
char = u;code = 117
char = a;code = 97
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char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
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char = c;code = 99
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char = a;code = 97
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char = c;code = 99
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char = d;code = 100
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char = s;code = 115
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char = s;code = 115
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char = e;code = 101
char = m;code = 109
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char = c;code = 99
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char = e;code = 101
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char = o;code = 111
char = s;code = 115
char = u;code = 117
char = r;code = 114
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char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = m;code = 109
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char = t;code = 116
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char = t;code = 116
char = r;code = 114
char = o;code = 111
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char = e;code = 101
char = .;code = 46
char = ;code = 32
char = W;code = 87
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char = t;code = 116
char = h;code = 104
char = ;code = 32
char = C;code = 67
char = s;code = 115
char = A;code = 65
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char = t;code = 116
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char = e;code = 101
char = a;code = 97
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char = t;code = 116
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char = o;code = 111
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char = o;code = 111
char = s;code = 115
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char = e;code = 101
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char = n;code = 110
char = e;code = 101
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char = c;code = 99
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char = e;code = 101
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char = a;code = 97
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char = b;code = 98
char = y;code = 121
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char = 7;code = 55
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char = ,;code = 44
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char = s;code = 115
char = p;code = 112
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char = v;code = 118
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char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = e;code = 101
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char = e;code = 101
char = f;code = 102
char = f;code = 102
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char = ;code = 32
char = a;code = 97
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char = 4;code = 52
char = 7;code = 55
char = %;code = 37
char = ;code = 32
char = a;code = 97
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char = ;code = 32
char = 1;code = 49
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char = ;code = 32
char = i;code = 105
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char = c;code = 99
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char = e;code = 101
char = a;code = 97
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char = m;code = 109
char = e;code = 101
char = a;code = 97
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char = A;code = 65
char = U;code = 85
char = C;code = 67
char = ;code = 32
char = f;code = 102
char = o;code = 111
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char = e;code = 101
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char = s;code = 115
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char = v;code = 118
char = e;code = 101
char = l;code = 108
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char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = w;code = 119
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char = a;code = 97
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char = e;code = 101
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char = o;code = 111
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char = s;code = 115
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char = a;code = 97
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char = i;code = 105
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char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = e;code = 101
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result sql = The purpose of this study was to assess the effect of the multidrug resistance modulator cyclosporine (CsA) on the pharmacokinetics of etoposide and mitoxantrone in children with de novo acute myeloid leukemia (AML). Serial blood samples for pharmacokinetic studies were obtained in 38 children over a 24-h period following cytotoxin treatment with or without CsA on days 1 and 4. Drug concentrations were quantitated using validated HPLC methods, and pharmacokinetic parameters were determined using compartmental modeling with an iterative two-stage approach, implemented on ADAPT II software. Etoposide displayed a greater degree of interindividual variability in clearance and systemic exposure than mitoxantrone. With CsA treatment, etoposide and mitoxantrone mean clearance declined by 71% and 42%, respectively. These effects on clearance, in combination with the empiric 40% dose reduction for either cytotoxin, resulted in a 47% and 12% increases in the mean AUC for etoposide and mitoxantrone, respectively. There were no differences in the rates of stomatitis or infection between the two groups. CsA treatment resulted in an increased incidence of hyperbilrubinemia, which rapidly reversed upon conclusion of drug therapy. The variability observed in clearance, combined with the empiric 40% dose reduction of the cytotoxins, resulted in statistically similar systemic exposure and similar toxicity.
Publication: Leukemia 2002 May ;16(5)::920-7.
Publication Date: 2002 May
Study Author(s): Lacayo, N J;Lum, B L;Becton, D L;Weinstein, H;Ravindranath, Y;Chang, M N;Bomgaars, L;Lauer, S J;Sikic, B I;Dahl, G V;
Institution: Divisions of Pediatric Hematology Oncology, Stanford University School of Medicine, Palo Alto, CA, USA.
Shortcut link to this study:
Publication Date: 2002 May
Study Author(s): Lacayo, N J;Lum, B L;Becton, D L;Weinstein, H;Ravindranath, Y;Chang, M N;Bomgaars, L;Lauer, S J;Sikic, B I;Dahl, G V;
Institution: Divisions of Pediatric Hematology Oncology, Stanford University School of Medicine, Palo Alto, CA, USA.
Shortcut link to this study:
The purpose of this study was to assess the effect of the multidrug resistance modulator cyclosporine (CsA) on the pharmacokinetics of etoposide and mitoxantrone in children with de novo acute myeloid leukemia (AML). Serial blood samples for pharmacokinetic studies were obtained in 38 children over a 24-h period following cytotoxin treatment with or without CsA on days 1 and 4. Drug concentrations were quantitated using validated HPLC methods, and pharmacokinetic parameters were determined using compartmental modeling with an iterative two-stage approach, implemented on ADAPT II software. Etoposide displayed a greater degree of interindividual variability in clearance and systemic exposure than mitoxantrone. With CsA treatment, etoposide and mitoxantrone mean clearance declined by 71% and 42%, respectively. These effects on clearance, in combination with the empiric 40% dose reduction for either cytotoxin, resulted in a 47% and 12% increases in the mean AUC for etoposide and mitoxantrone, respectively. There were no differences in the rates of stomatitis or infection between the two groups. CsA treatment resulted in an increased incidence of hyperbilrubinemia, which rapidly reversed upon conclusion of drug therapy. The variability observed in clearance, combined with the empiric 40% dose reduction of the cytotoxins, resulted in statistically similar systemic exposure and similar toxicity.
PMID: 11986955
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