Summary
Repeated methotrexate absorption studies were performed under standard conditions in 127 children receiving either oral or intramuscular methotrexate for acute lymphoblastic leukaemia. There was marked variability in peak concentration, area under the serum concentration curve and clearance both between patients and in repeated studies on the same patient. Although the intramuscular route produced higher serum concentrations and AUC than the oral route, variability within and between patients was considerable and was most marked at higher concentrations. Neither age or sex could account for variation in methotrexate absorption or clearance.
Intramuscular methotrexate, although producing higher serum concentrations and AUC, does not reduce the variability observed with oral administration. Prediction of subsequent methotrexate concentrations from the knowledge of one absorption profile is not possible.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Balis FM, Savitch JL, Bleyer WA (1983) Pharmacokinetics of oral methotrexate in children. Cancer Res 43: 2342–2345
Chan H, Evans WE, Pratt CB (1977) Recovery from toxicity associated with high dose methotrexate prognostic factors. Cancer Treat Rep 61: 797–804
Chessells JM, Leiper AD, Tiedeman K, Hardisty RM, Richards S (1987) Oral methotrexate is as effective as intramuscular methotrexate in maintenance therapy of acute lymphoblastic leukaemia. Arch Dis Child 62: 172–176
Craft AW, Kay HEM, Lawson DN, McElwain TJ (1977) Methotrexate-induced malabsorption in children with acute lymphoblastic leukaemia. Br Med J 2: 1511–1512
Craft AW, Rankin A, Aherne W (1980) Methotrexate absorption in children with acute lymphoblastic leukaemia. Cancer Treat Rep S1: 65: 77–81
Dickinson-Gibbons J (1985) Non parametric methods for quantitative analysis. Second edition. American Sciences Press Inc, Ohio, pp 250–254
Evans WE, Crom WR, Stewart CF et al. (1984) Methotrexate systemic clearance influences the probability of relapse in children with standard risk acute lymphocytic leukaemia. Lancet I: 359–362
Evans WE, Crom WR, Abromowitch M et al. (1986) Clinical pharmacodynamics of high-dose methotrexate in acute lymphocytic leukaemia. N Engl J Med 314: 471–477
Freeman-Narrod M (1962) The pharmacology of methotrexate. Porter R, Wiltshaw E (eds) Methotrexate in the treatment of cancer. Williams and Wilkins, Baltimore, pp 17–21
Gushaw JB, Miller JG (1978) Homogenous enzyme immunoassay for methotrexate in serum. Clin Chem 24: 1032
Harvey VJ, Slevin ML, Joel SP et al. (1985) Variable bioavailability following repeated oral doses of etoposide. Eur J Cancer Clin Oncol 21: 1315–1319
Kearney PJ, Light PA, Preece A, Mott MG (1979) Unpredictable serum levels after oral methotrexate in children with acute lymphoblastic leukaemia. Cancer Chemother Pharmacel 3: 117–120
Pearson ADJ, Craft AW, Pledger JV, Eastham EJ, Laker MF, Pearson GL (1984) Small bowel function in acute lymphoblastic leukaemia. Arch Dis Child 59: 460–465
Pearson ADJ, Craft AW, Eastham EJ et al. (1985) Small intestinal transit time affects methotrexate absorption in children with acute lymphoblastic leukaemia. Cancer Chemother Pharmacol 14: 211–215
Perkkio M, Rajantie J, Savilahti E, Siimes MA (1984) Jejunal mucosa after leukaemia treatment in children. Acta Paed Scand 73: 680–684
Pinkerton CR, Welshman SG, Dempsey SI, Bridges JM, Glasgow JFT (1980) Absorption of methotrexate under standardised conditions in children with acute lymphoblastic leukaemia. Br J Cancer 42: 613–615
Pinkerton CR, Welshman SG, Glasgow JFT, Bridges JM (1980) Can food influence the absorption of methotrexate in children with acute lymphoblastic leukaemia? Lancet II: 944–946
Pinkerton CR, Glasgow JFT, Bridges JM, Welshman SG (1981) Enterotoxic effect of methotrexate: does it influence the drug's absorption in children with acute lymphoblastic leukaemia? Br Med J 282: 1276–1277
Pinkerton CR, Welshman SG, Kelly JG, Shanks RG, Bridges JM (1982) Pharmacokinetics of low dose methotrexate in children receiving maintenance therapy for acute lymphoblastic leukaemia. Cancer Chemother Pharmacol 10: 36–39
Rivard GE, Infante-Rivard C, Hoyoux C, Champagne J (1985) Maintenance chemotherapy for childhood acute lymphoblastic leukaemia: better in the evening. Lancet 2: 1264–1266
Schrogie JJ, Davies RO, Hwang SS et al. (1979) Intrasubject variability in methyldopa bioavailability. Clin Pharmacol Ther 32: 248
Smith SD, Rosen D, Trueworthy RC, Lowman JT (1979) A reliable method for evaluating drug compliance in children with cancer. Cancer 43: 169–173
Smith DK, Omura GA, Ostroy F (1980) Clinical pharmacology of intermediate dose oral methotrexate. Cancer Chemother Pharmacol 4: 117–120
Steele WH, Stuart JFB, Lawrence JR et al. (1979) Enhancement of methotrexate absorption by subdivision of dose. Cancer Chemother Pharmacol 3: 235–237
Taminiau JAJM, Gall DG, Hamilton JR (1980) Response of the rat small intestine epithelium to methotrexate. Gut 21: 486–492
Trier JS (1962) Morphologic alterations induced by methotrexate in the mucosa of human proximal intestine. I. Serial observations by light microscopy. Gastroenterology 42: 295–305
Walson PD, Strunk RC, Taussig LM (1977) Intrapatient variability in theophylline kinetics. J Ped 91: 321–324
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pearson, A.D.J., Mills, S., Amineddine, H.A. et al. Pharmacokinetics of oral and intramuscular methotrexate in children with acute lymphoblastic leukaemia. Cancer Chemother. Pharmacol. 20, 243–247 (1987). https://doi.org/10.1007/BF00570494
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00570494