Pharmacokinetics of methotrexate and its 7-OH metabolite in cancer patients treated with different high-methotrexate dosage regimens
✍ Scribed by Adnan Ei-Yazigi; Magid Amer; Iman Al-Saleh; Cazemiro Martin
- Publisher
- John Wiley and Sons
- Year
- 1986
- Tongue
- French
- Weight
- 534 KB
- Volume
- 38
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
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 mglkg (A), 80 mglkg preceded by 20 mglkg i.v. loading dose (B), and 70 mg/kg preceded by 30 mglkg 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 2compartment model with overall mean f SD for beta, k12, k2,, and kI3 of 0.225,f0.196, l.33& 1.44, 0.954 f I .06, and 0.994 & I .28 hr -, respectively. The total body clearance, V,, and V-beta were 0.123 & 0.037 I/hr.kg, 0. I 5 f 0.122 Ilkg, and 0.965 & 0.875 Ilkg, respectively. No significant differences @>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, I I .5, and 9.2 hr and the mean f SD values of these concentrations were 15.02k 14, 18.96& 13.63, 14.91 & 9.95 p ~, respectively. With regimens A and C, maximum observed concentrations of MX equal to 231 & 67. I and 204 +-69.5 p~ occurred at 0.5 and 6 hr, respectively. Only with regimen B was a steady-state MX concentration of 179 p~ achieved throughout infusion; this regimen is therefore highly advantageous for highdose MX treatment.