Urine volume to hydration volume ratio is associated with pharmacokinetics of high-dose methotrexate in patients with primary central nervous system lymphoma.

1. Brain Tumor Registry of Japan (2005-­2008). Neurol Med Chir.

2017;57(suppl 1):9-­102. doi:10.2176/nmc.sup.2017-­0 001

2. Panageas KS, Elkin EB, DeAngelis LM, Ben-­Porat L, Abrey LE. Trends

in survival from primary central nervous system lymphoma, 1975–­

1999: a population-­based analysis. Cancer. 2005;104(11):2466-­

2472. doi:10.1002/cncr.21481

3. Hiraga S, Arita N, Ohnishi T, et al. Rapid infusion of high-­dose

methotrexate resulting in enhanced penetration into cerebrospinal fluid and intensified tumor response in primary central nervous

system lymphomas. J Neurosurg. 1999;91(2):221-­230. doi:10.3171/

jns.1999.91.2.0221

4. O’Brien PC, Roos DE, Pratt G, et al. Combined-­modality therapy for primary central nervous system lymphoma: long-­term

data from a Phase II multicenter study (Trans-­Tasman Radiation

Oncology Group). Int J Radiat Oncol Biol Phys. 2006;64(2):408-­413.

doi:10.1016/j.ijrobp.2005.07.958

5. Jahnke K, Doolittle ND, Muldoon LL, Neuwelt EA. Implications

of the blood-­brain barrier in primary central nervous system

lymphoma. Neurosurg Focus. 2006;21(5):1-­11. doi:10.3171/

foc.2006.21.5.12

6. Stoller RG, Hande KR, Jacobs SA, Rosenberg SA, Chabner BA. Use

of plasma pharmacokinetics to predict and prevent methotrexate

10 of 11 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. toxicity. N Engl J Med. 1977;297(12):630-­634. doi:10.1056/nejm1​

97709​22297​1203

Widemann BC, Balis FM, Kempf-­Bielack B, et al. High-­dose

methotrexate-­induced nephrotoxicity in patients with osteosarcoma: incidence, treatment, and outcome. Cancer.

2004;100(10):2222-­2232. doi:10.1002/cncr.20255

Nirenberg A, Mosende C, Mehta BM, Gisolfi AL, Rosen G. High

dose methotrexate with citrovorum factor rescue: predictive value

of serum methotrexate concentrations and corrective measures

to avert toxicity. Cancer Treat Rep. 1977;61(5):779-­783. https://

pubmed.ncbi.nlm.nih.gov/30214​3/

Sakura T, Hayakawa F, Sugiura I, et al. High-­dose methotrexate

therapy significantly improved survival of adult acute lymphoblastic leukemia: a phase III study by JALSG. Leukemia. 2018;32(3):626-­

632. doi:10.1038/leu.2017.283

Comandone A, Passera R, Boglione A, Tagini V, Ferrari S, Cattel L.

High dose methotrexate in adult patients with osteosarcoma: clinical and pharmacokinetic results. Acta Oncol. 2005;44(4):406-­411.

doi:10.1080/02841​86051​0 029770

Zhu J-­J, Gerstner ER, Engler DA, et al. High-­dose methotrexate

for elderly patients with primary CNS lymphoma. Neuro Oncol.

2009;11(2):211-­215. doi:10.1215/15228​517-­2008-­067

Baxmann AC, Ahmed MS, Marques NC, et al. Influence of muscle mass and physical activity on serum and urinary creatinine

and serum cystatin C. Clin J Am Soc Nephrol. 2008;3(2):348-­354.

doi:10.2215/CJN.02870707

Burkhardt H, Bojarsky G, Gretz N, Gladisch R. Creatinine clearance,

Cockcroft-­Gault formula and cystatin C: estimators of true glomerular filtration rate in the elderly? Gerontology. 2002;48(3):140-­146.

doi:10.1159/00005​2832

Zhang W, Zhang Q, Tian X, et al. Population pharmacokinetics

of high-­dose methotrexate after intravenous administration in

Chinese osteosarcoma patients from a single institution. Chin Med

J. 2015;128(1):111-­118. doi:10.4103/0366-­6999.147829

Panetta JC, Roberts JK, Huang J, et al. Pharmacokinetic basis for

dosing high-­dose methotrexate in infants and young children with

malignant brain tumours. Br J Clin Pharmacol. 2020;86(2):362-­371.

doi:10.1111/bcp.14160

Ye M, Fu Q, Li P, Zhu Z. High dose methotrexate population pharmacokinetics and Bayesian estimation in patients with lymphoid malignancy. Biopharm Drug Dispos. 2009;30(8):437-­4 47. doi:10.1002/

bdd.678

Dupuis C, Mercier C, Yang C, et al. High-­dose methotrexate in

adults with osteosarcoma: a population pharmacokinetics study

and validation of a new limited sampling strategy. Anticancer Drugs.

2008;19(3):267-­273. doi:10.1097/CAD.0b013​e3282​f21376

Kawakatsu S, Nikanjam M, Lin M, et al. Population pharmacokinetic

analysis of high-­dose methotrexate in pediatric and adult oncology patients. Cancer Chemother Pharmacol. 2019;84(6):1339-­1348.

doi:10.1007/s0028​0 -­019-­03966​- ­4

Mei S, Li X, Jiang X, Yu K, Lin S, Zhao Z. Population pharmacokinetics of high-­dose methotrexate in patients with primary central

nervous system lymphoma. J Pharm Sci. 2018;107(5):1454-­1460.

doi:10.1016/j.xphs.2018.01.004

Cockcroft DW, Gault MH. Prediction of creatinine clearance from

serum creatinine. Nephron. 1976;16(1):31-­41. doi:10.1159/00018​

0580

Thyss A, Kubar J, Milano G, Namer M, Schneider M. Clinical and

pharmacokinetic evidence of a life-­threatening interaction between methotrexate and ketoprofen. Lancet. 1986;1(8475):256-­

258. doi:10.1016/S0140​-­6736(86)90786​-­5

Suzuki K, Doki K, Homma M, et al. Co-­administration of proton

pump inhibitors delays elimination of plasma methotrexate in high-­

dose methotrexate therapy. Br J Clin Pharmacol. 2009;67(1):44-­49.

doi:10.1111/j.1365-­2125.2008.03303.x

ISONO et al.

23. Bain E, Birhiray RE, Reeves DJ. Drug-­drug interaction between

methotrexate and levetiracetam resulting in delayed methotrexate elimination. Ann Pharmacother. 2014;48(2):292-­296.

doi:10.1177/10600​28013​511951

24. Inose R, Takahashi K, Nanno S, Hino M, Nagayama K. Calcium channel blockers possibly delay the elimination of plasma methotrexate

in patients receiving high-­dose methotrexate therapy. J Chemother.

2019;31(1):30-­3 4. doi:10.1080/11200​09X.2018.1544194

25. Beal SL. Ways to fit a PK model with some data below the quantification limit. J Pharmacokinet Pharmacodyn. 2001;28(5):481-­504.

doi:10.1023/A:10122​99115260

26. Bergstrand M, Karlsson MO. Handling data below the limit of

quantification in mixed effect models. AAPS J. 2009;11(2):371-­380.

doi:10.1208/s1224​8-­0 09-­9112-­5

27. Lindbom L, Pihlgren P, Jonsson N. PsN-­Toolkit -­ a collection of

computer intensive statistical methods for non-­linear mixed effect modeling using NONMEM. Comput Methods Programs Biomed.

2005;79(3):241-­257. doi:10.1016/j.cmpb.2005.04.005

28. Fukuhara K, Ikawa K, Morikawa N, Kumagai K. Population pharmacokinetics of high-­dose methotrexate in Japanese adult patients with malignancies: a concurrent analysis of the serum and

urine concentration data. J Clin Pharm Ther. 2008;33(6):677-­684.

doi:10.1111/j.1365-­2710.2008.00966.x

29. Hui KH, Chu HM, Fong PS, Cheng WTF, Lam TN. Population pharmacokinetic study and individual dose adjustments of high-­dose

methotrexate in Chinese pediatric patients with acute lymphoblastic leukemia or osteosarcoma. J Clin Pharmacol. 2019;59(4):566-­

577. doi:10.1002/jcph.1349

3 0. Taylor ZL, Mizuno T, Punt NC, et al. MTXPK.org: a clinical decision

support tool evaluating high-­dose methotrexate pharmacokinetics

to inform post-­infusion care and use of glucarpidase. Clin Pharmacol

Ther. 2020;108(3):635-­6 43. doi:10.1002/cpt.1957

31. Gerber DE, Grossman SA, Batchelor T, Ye X. Calculated versus measured creatinine clearance for dosing methotrexate in the treatment

of primary central nervous system lymphoma. Cancer Chemother

Pharmacol. 2007;59(6):817-­823. doi:10.1007/s0028​0-­0 06-­0339-­x

32. Bjornsson TD. Use of serum creatinine concentrations to determine renal function1. Clin Pharmacokinet. 1979;4(3):200-­222.

doi:10.2165/00003​0 88-­19790​4 030-­0 0003

33. Gaspari F, Perico N, Remuzzi G. Application of newer clearance

techniques for the determination of glomerular filtration rate. Curr

Opin Nephrol Hypertens. 1998;7(6):675-­680. doi:10.1097/00041​

552-­19981​1000-­0 0009

3 4. Steele WH, Lawrence JR, Stuart JFB, McNeill CA. The protein binding of methotrexate in the serum of patients with neoplastic disease. Cancer Chemother Pharmacol. 1981;7(1):61-­6 4. doi:10.1007/

BF002​58215

35. Bratlid D, Moe PJ. Pharmacokinetics of high-­dose methotrexate

treatment in children. Eur J Clin Pharmacol. 1978;14(2):143-­147.

doi:10.1007/BF006​07446

36. Omuro A, Chinot O, Taillandier L, et al. Methotrexate and temozolomide versus methotrexate, procarbazine, vincristine, and cytarabine

for primary CNS lymphoma in an elderly population: an intergroup

ANOCEF-­GOELAMS randomised phase 2 trial. Lancet Haematol.

2015;2(6):e251-­e259. doi:10.1016/S2352​-­3 026(15)00074​-­5

37. Fritsch K, Kasenda B, Schorb E, et al. High-­dose methotrexate-­

based immuno-­chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study). Leukemia. 2017;31(4):846-­852.

doi:10.1038/leu.2016.334

38. Christensen ML, Rivera GK, Crom WR, Hancock ML, Evans WE.

Effect of hydration on methotrexate plasma concentrations in children with acute lymphocytic leukemia. J Clin Oncol. 1988;6(5):797-­

801. doi:10.1200/JCO.1988.6.5.797

39. Traivaree C, Likasitthananon N, Monsereenusorn C, Rujkijyanont

P. The effect of intravenous hydration strategy on plasma

11 of 11

ISONO et al.

4 0. 41. 42. 43. 4 4. 45. 46. methotrexate clearance during intravenous high-­dose methotrexate administration in pediatric oncology patients. Cancer Manag

Res. 2018;10:4471-­4 478. doi:10.2147/CMAR.S172117

Howard SC, McCormick J, Pui C, Buddington RK, Harvey RD.

Preventing and managing toxicities of high-­dose methotrexate.

Oncologist.

2016;21(12):1471-­1482.

doi:10.1634/theon​colog​

ist.2015-­0164

Abelson HT, Fosburg MT, Beardsley GP, et al. Methotrexate-­

induced renal impairment: clinical studies and rescue from systemic

toxicity with high-­dose leucovorin and thymidine. J Clin Oncol.

1983;1(3):208-­216. doi:10.1200/JCO.1983.1.3.208

Widemann BC, Adamson PC. Understanding and managing

methotrexate nephrotoxicity. Oncologist. 2006;11(6):694-­703.

doi:10.1634/theon​colog​ist.11-­6-­694

Ramsey LB, Panetta JC, Smith C, et al. Genome-­wide study of methotrexate clearance replicates SLCO1B1. Blood. 2013;121(6):898-­

904. doi:10.1182/blood​-­2012-­0 8-­452839

Chen M, Chen W, Liu P, et al. The impacts of gene polymorphisms

on methotrexate in Chinese psoriatic patients. J Eur Acad Dermatol

Venereol. 2020;34(9):2059-­2065. doi:10.1111/jdv.16440

Vlaming MLH, van Esch A, van de Steeg E, et al. Impact of

Abcc2 [multidrug resistance-­associated protein (Mrp) 2], Abcc3

(Mrp3), and Abcg2 (breast cancer resistance protein) on the

oral pharmacokinetics of methotrexate and its main metabolite

7-­hydroxymethotrexate. Drug Metab Dispos. 2011;39(8):1338-­

1344. doi:10.1124/dmd.111.038794

Ueshima S, Hira D, Kimura Y, et al. Population pharmacokinetics

and pharmacogenomics of apixaban in Japanese adult patients

with atrial fibrillation. Br J Clin Pharmacol. 2018;84(6):1301-­1312.

doi:10.1111/bcp.13561

47. Nakanishi T, Tamai I. Genetic polymorphisms of OATP transporters and their impact on intestinal absorption and hepatic disposition of drugs. Drug Metab Pharmacokinet. 2012;27(1):106-­121.

doi:10.2133/dmpk.dmpk-­11-­r v-­099

48. Reeves DJ, Moore ES, Bascom D, Rensing B. Retrospective evaluation of methotrexate elimination when co-­administered with

proton pump inhibitors. Br J Clin Pharmacol. 2014;78(3):565-­571.

doi:10.1111/bcp.12384

49. Riva M. Brain tumoral epilepsy: a review. Neurol Sci. 2005;26(suppl

1):40-­42. doi:10.1007/s1007​2-­0 05-­0 404-­y

S U P P O R T I N G I N FO R M AT I O N

Additional supporting information may be found in the online version of the article at the publisher’s website.

How to cite this article: Isono T, Hira D, Morikochi A, et al.

Urine volume to hydration volume ratio is associated with

pharmacokinetics of high-­dose methotrexate in patients with

primary central nervous system lymphoma. Pharmacol Res

Perspect. 2021;9:e00883. doi:10.1002/prp2.883

...