Pharmacokinetics of Very High-Dose Oral Melphalan in Cancer Patients
| Autor: | Thomas L. Goodman, David S. Alberts, Thomas E. Penn, Robert F. Asbury, Laszlo Boros, Yei-Mei Peng, Doris E. Hickox |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Adult
Male Melphalan Cancer Research medicine.medical_specialty Time Factors Lymphoma Bone marrow transplantation Microgram Urology Administration Oral Biological Availability Adenocarcinoma Bolus (medicine) Pharmacokinetics Oral administration hemic and lymphatic diseases Antineoplastic Combined Chemotherapy Protocols medicine Humans Melanoma neoplasms Etoposide Bone Marrow Transplantation business.industry Middle Aged Carmustine Surgery medicine.anatomical_structure Oncology Injections Intravenous Female Bone marrow business medicine.drug |
| Zdroj: | American Journal of Clinical Oncology. 13:19-22 |
| ISSN: | 0277-3732 |
| DOI: | 10.1097/00000421-199002000-00006 |
| Popis: | 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 micrograms/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 micrograms.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. |
| Databáze: | OpenAIRE |
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