TY - JOUR
T1 - Pharmacokinetics of very high-dose oral melphalan in cancer patients
AU - Boros, L.
AU - Peng, Y. M.
AU - Alberts, D. S.
AU - Asbury, R. F.
AU - Goodman, T. L.
AU - Penn, T. E.
AU - Hickox, D. E.
PY - 1990
Y1 - 1990
N2 - The pharmacokinetics and systemic availability of melphalan after high-dose oral administration with and without 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or etoposide were examined in three patients undergoing autologous bone marrow transplantation. Patient 1 (advanced melanoma) received melphalan at 80 mg/m2/day p.o. on days -6, -5, and -4, followed by BCNU at 300 mg/m2/day i.v. on days -3, -2, and -1 prior to bone marrow transplantation. Patient 2 (advanced colon carcinoma) received melphalan at 75 mg/m2/day p.o. on days -3, -2, and -1. Patient 3 (advanced refractory lymphoma) received etoposide at 800 mg/m2/day i.v. on days -7, -5, and -3, followed by melphalan at 157 mg/m2/day p.o. on days -2 and -1. Melphalan was administered as a bolus oral dose, using 2-mg tablets. Blood samples were collected at 0, 5, 10, 15, 30, and 45 min and 1, 2, 3, 4, 6, 8, 12, and 24 h after each dose of melphalan. Peak plasma melphalan concentrations in the three patients ranged from 0.354 (patient 2) to 1.768 μg/ml (patient 1). Plasma melphalan concentration x time products (C x Ts) showed extreme variability in one patient (patient 2), ranging from 0.76 to 4.48 μg·h/ml. To determine the relative systemic availability of orally administered melphalan, i.v. C x Ts proportional to the p.o. doses were extrapolated from previously reported i.v. bolus pharmacokinetic data. The p.o.:i.v. plasma C x T ratios for high-dose melphalan ranged between 0.09 (patient 3) and 0.58 (patient 2). Although these C x T data suggest a dose-response for orally administered melphalan, the systemic availability of these high p.o. melphalan doses was extremely variable, both within and between study patients. Thus, we cannot recommend the use of high-dose p.o. melphalan regimens in patients undergoing autologous bone marrow transplantation.
AB - The pharmacokinetics and systemic availability of melphalan after high-dose oral administration with and without 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or etoposide were examined in three patients undergoing autologous bone marrow transplantation. Patient 1 (advanced melanoma) received melphalan at 80 mg/m2/day p.o. on days -6, -5, and -4, followed by BCNU at 300 mg/m2/day i.v. on days -3, -2, and -1 prior to bone marrow transplantation. Patient 2 (advanced colon carcinoma) received melphalan at 75 mg/m2/day p.o. on days -3, -2, and -1. Patient 3 (advanced refractory lymphoma) received etoposide at 800 mg/m2/day i.v. on days -7, -5, and -3, followed by melphalan at 157 mg/m2/day p.o. on days -2 and -1. Melphalan was administered as a bolus oral dose, using 2-mg tablets. Blood samples were collected at 0, 5, 10, 15, 30, and 45 min and 1, 2, 3, 4, 6, 8, 12, and 24 h after each dose of melphalan. Peak plasma melphalan concentrations in the three patients ranged from 0.354 (patient 2) to 1.768 μg/ml (patient 1). Plasma melphalan concentration x time products (C x Ts) showed extreme variability in one patient (patient 2), ranging from 0.76 to 4.48 μg·h/ml. To determine the relative systemic availability of orally administered melphalan, i.v. C x Ts proportional to the p.o. doses were extrapolated from previously reported i.v. bolus pharmacokinetic data. The p.o.:i.v. plasma C x T ratios for high-dose melphalan ranged between 0.09 (patient 3) and 0.58 (patient 2). Although these C x T data suggest a dose-response for orally administered melphalan, the systemic availability of these high p.o. melphalan doses was extremely variable, both within and between study patients. Thus, we cannot recommend the use of high-dose p.o. melphalan regimens in patients undergoing autologous bone marrow transplantation.
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U2 - 10.1097/00000421-199002000-00006
DO - 10.1097/00000421-199002000-00006
M3 - Article
C2 - 2305718
AN - SCOPUS:0025237063
VL - 13
SP - 19
EP - 22
JO - American Journal of Clinical Oncology
JF - American Journal of Clinical Oncology
SN - 0277-3732
IS - 1
ER -