Methotrexate pharmacokinetics

Beach BJ, Woods WG, Howell SB. Influence of cotrimoxazole on methotrexate pharmacokinetics in children with acute lymphoblastic leukemia. Am J Pediatr Hematol Oncol 1981 3 115-119. 

Larsen FG, Nielsen-Kudsk F, Jakobsen P, Schroder H, Kragballe K. Interaction of etretinate with methotrexate pharmacokinetics in psoriatic patients. J Clin Pharmacol 1990 30(9) 802-7. 

Koerber H, Gross WL, Iven H. Do steroids influence low dose methotrexate pharmacokinetics J Rheumatol 1994 21(6) 1170-2. 

Combe B, Edno L, Lafforgue P, Bologna C, Bernard JC, Acquaviva P, Sany J, Bressolle F. Total and free methotrexate pharmacokinetics, with and without piroxicam, in rheumatoid arthritis patients. Br J Rheumatol 1995 34(5) 421-8. 

A literature review of interactions between methotrexate and NSAIDs found that low-dose methotrexate pharmacokinetics were unaltered by NSAIDs, with the exception of salicylates. ... 

An a J-M, Fabre D, BressoUe F, Bolc na C, Alric R, Cocciglio M, Dropsy R, Sany J. Effect of etodolac on methotrexate pharmacokinetics in patients with rheumatoid arthritis. J Rheumatol (1994)21,203-S. 

Bischoff KB, Dedrick RL, Zaharko DS, Longstreth JA. Methotrexate pharmacokinetics. / Pharm Sci 1971 60 1128-1133. 

JM Weissbrod. A comprehensive approach to whole body pharmacokinetics in mammalian systems Applications to methotrexate, streptozotocin and zinc. DSc Eng dissertation, Columbia University, New York, 1979, pp 110-112. 

JM Weissbrod, RK Jain, FM Sirotnak. Pharmacokinetics of methotrexate in leukemia cells Effect of dose and mode of injection. J Pharmacokin Biopharm 6 487-503, 1978. 

If the unbound drug concentrations in plasma are higher than their K values on the transporters, then transporter function may be significantly affected [106], Following a pharmacokinetic analysis of the effect of probenecid on the hepatobiliary excretion of methotrexate, it has been shown the extent of an in vivo drug-drug interaction can be quantitatively predicted from the kinetic parameters for transport across the sinusoidal and bile canalicular membranes determined in vitro [107]. 

In a Phase la study in healthy volunteers, ARRY-438162 was well tolerated up to 20mg/kg q.d. oral dose. There was a dose proportional increase in plasma concentration and decrease in the production of IL-1 ft, TNFa, IL-6 and pERK in the ex-vivo-stimulated whole blood from drug treated volunteers. Array has initiated a Phase lb study of ARRY-438162 in combination with methotrexate in rheumatoid arthritis patients with the goals of assessing safety, tolerability, pharmacokinetics (PK), biomarkers and initial signs of efficacy. 

Balis FM, Holcenberg JS, Poplack DG et al. Pharmacokinetics and pharmacodynamics of oral methotrexate and mercaptopurine in children with lower risk acute lymphoblastic leukemia a joint Childrens Cancer Group and Pediatric Oncology Branch study. Blood 1998 92 3569-3577. 

Andersen JB, Szumlanski C, Weinshilboum RM et al. Pharmacokinetics, dose adjustments, and 6-mercaptopurine/methotrexate drug interactions in two patients with thiopurine methyltransferase deficiency. Acta Paediatr 1998 87 108-111. 

R. Sett, H. S. Sarkar, and P. K. Das, Pharmacokinetics and biodistribution of methotrexate conjugated to mannosyl human serum albumin, J. Antimicrob. Chemother. 37 151-159 (1993). 

Breedveld P, Zelcer N, Pluim D, et al. Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles potential role for breast cancer resistance protein in clinical drug-drug interactions. Cancer Res 2004 64 5804— 5811. 

QSAR analysis of studies at the cellular level allows us to get a handle on the physicochemical parameters critical to pharmacokinetics processes, mostly transport. Cell culture systems offer an ideal way to determine the optimum hydrophobicity of a system that is more complex than an isolated receptor. Extensive QSAR have been developed on the toxicity of 3-X-triazinesto many mammalian and bacterial cell lines (202, 209). A comparison of the cytotoxicities of these analogs vs. sensitive murine leukemia cells (L1210/S) and methotrexate-resistant murine leukemia cells (L1210/R) reveals some startling differences. 

Bleyer WA. Clinical pharmacology of intrathecal methotrexate. II. An improved dosage regimen derived from age-related pharmacokinetics. Cancer Treat Rep 1977 61 1419-25. 

Bleyer WA, Coccia PF, Sather HN, Level C, Lukens J, Niebrugge DJ et al. Reduction in central nervous system leukemia with a pharmacokinetically dervived intrathecal methotrexate dosage regimen. J Clin Oncol 1983 1 317-25. 

A 17-year-old girl with a femoral osteosarcoma received her 11th cycle of methotrexate and simultaneously oral doxycycline 100 mg bd for a palpebral abscess. As in previous cycles, pharmacokinetic monitoring of methotrexate was performed. On this occasion the half-life of methotrexate was more than doubled. She developed hematological and gastroenterological toxicity. 

In 13 patients with rheumatoid arthritis, oral meloxicam for 1 week had no effect on the pharmacokinetics of a single dose of intravenous methotrexate 15 mg (18). 

Hubner G, Sander O, Degner FL, Turck D, Rau R. Lack of pharmacokinetic interaction of meloxicam with methotrexate in patients with rheumatoid arthritis. J Rheumatol... 

A case of severe hepatitis has been attributed to the combination of methotrexate with etretinate (134), a finding that was not explained by a pharmacokinetic interaction between the two drugs (135). 

Lafforgue P, Monjane 1-Mouterde S, Durand A, Catalin J, Acquaviva PC. Is there an interaction between low doses of corticosteroids and methotrexate in patients with rheumatoid arthritis A pharmacokinetic study in 33 patients. J Rheumatol 1993 20(2) 263-7. 

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