Abstract:
:The pharmacokinetics of methotrexate (MX) and 7-OH methotrexate (MXOH) was studied in 18 cancer patients treated with 6-hr intravenous (i.v.) infusion of 100 mg/kg (A), 80 mg/kg preceded by 20 mg/kg i.v. loading dose (B), and 70 mg/kg preceded by 30 mg/kg i.v. loading dose (C). Simultaneous analysis of MX and MXOH was performed by high-performance liquid chromatography. The data for MX conformed to a 2-compartment model with overall mean +/- SD for beta, k12, k21, and k13 of 0.225 +/- 0.196, 1.33 +/- 1.44, 0.954 +/- 1.06, and 0.994 +/- 1.28 hr-1, respectively. The total body clearance, Vc, and V-beta were 0.123 +/- 0.037 l/hr.kg, 0.15 +/- 0.122 l/kg, and 0.965 +/- 0.875 l/kg, respectively. No significant differences (p greater than 0.05) in these parameters, attributable to the difference in regimens, were observed. With regimens A, B and C, the maximum observed concentrations of MXOH occurred at 9.2, 11.5, and 9.2 hr and the mean +/- SD values of these concentrations were 15.02 +/- 14, 18.96 +/- 13.63, 14.91 +/- 9.95 microM, respectively. With regimens A and C, maximum observed concentrations of MX equal to 231 +/- 67.1 and 204 +/- 69.5 microM occurred at 0.5 and 6 hr, respectively. Only with regimen B was a steady-state MX concentration of 179 microM achieved throughout infusion; this regimen is therefore highly advantageous for high-dose MX treatment.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
el-Yazigi A,Amer M,Al-Saleh I,Martin Cdoi
10.1002/ijc.2910380603subject
Has Abstractpub_date
1986-12-15 00:00:00pages
795-800issue
6eissn
0020-7136issn
1097-0215journal_volume
38pub_type
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journal_title:International journal of cancer
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