TY - JOUR
T1 - Effect of hepatic dysfunction on oral cyclosporine pharmacokinetics in marrow transplant patients
AU - Yee, G. C.
AU - Kennedy, M. S.
AU - Storb, R.
AU - Thomas, E. D.
PY - 1984
Y1 - 1984
N2 - The effect of hepatic dysfunction, defined as abnormal serum bilirubin level, on oral cyclosporine (CSP) pharmacokinetics was examined in 28 marrow transplant patients who received CSP for prophylaxis of graft-v-host disease. Serum CSP concentrations were measured by radioimmunoassay. Forty-one concentration-time courses were studied, divided among patients with no (<1.2 mg/dL), mild (1.2 to 2.0 mg/dL), and moderate (2.0 to 5.0 mg/dL) hepatic dysfunction. CSP elimination, as determined by elimination rate constant and clearance, was delayed in patients with moderate hepatic dysfunction compared to those with no hepatic dysfunction (P <.05). The volume of distribution, lag time for absorption, maximum serum concentration, and time at which the maximum concentration was achieved was not affected by hepatic function. These data indicate that patients with moderate hepatic dysfunction have delayed CSP or CSP metabolite elimination and may be at higher risk for developing CSP-related toxicity.
AB - The effect of hepatic dysfunction, defined as abnormal serum bilirubin level, on oral cyclosporine (CSP) pharmacokinetics was examined in 28 marrow transplant patients who received CSP for prophylaxis of graft-v-host disease. Serum CSP concentrations were measured by radioimmunoassay. Forty-one concentration-time courses were studied, divided among patients with no (<1.2 mg/dL), mild (1.2 to 2.0 mg/dL), and moderate (2.0 to 5.0 mg/dL) hepatic dysfunction. CSP elimination, as determined by elimination rate constant and clearance, was delayed in patients with moderate hepatic dysfunction compared to those with no hepatic dysfunction (P <.05). The volume of distribution, lag time for absorption, maximum serum concentration, and time at which the maximum concentration was achieved was not affected by hepatic function. These data indicate that patients with moderate hepatic dysfunction have delayed CSP or CSP metabolite elimination and may be at higher risk for developing CSP-related toxicity.
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U2 - 10.1182/blood.v64.6.1277.1277
DO - 10.1182/blood.v64.6.1277.1277
M3 - Article
C2 - 6388664
AN - SCOPUS:0021684957
SN - 0006-4971
VL - 64
SP - 1277
EP - 1279
JO - Blood
JF - Blood
IS - 6
ER -