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Pharmacokinetics of methotrexate and its 7‐OH metabolite in cancer patients treated with different high‐methotrexate dosage regimens
Author(s) -
EiYazigi Adnan,
Amer Magid,
AlSaleh Iman,
Martin Cazemiro
Publication year - 1986
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910380603
Subject(s) - methotrexate , pharmacokinetics , metabolite , regimen , antifolate , medicine , chemistry , pharmacology , antimetabolite
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 (S), 80 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 , repectively. The total body clearance, Vc, and V‐beta were 0.123 ± 0.037 1/hr.kg, 0.15 ± 0.122 l/kg, and 0.965 ± 0.87 l/kg, respectively. No significant differences ( p > 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 ± 14.91 ± 9.95 μm, respectively. With regimens A and C, maximum obserced concentration of MX equal to 231 ± 67.1 and 204 ± 69.5 μm, occurred at 0.5 and 6 hr, respectively. Only with regimen B was a steady‐state MX concnetration of 179 μm, achieved throughout infusion; this regimen is therefore highly advantageours for high‐dose MX treatment.