Low dose pulse methotrexate (LDMTX) therapy has become effective in the treatment of autoimmune and lymphoproliferative diseases. The pharmacokinetics of LDMTX is individually highly variable, resulting in a different systemic exposure to the drug and a variable therapeutic/toxic effect in patients. The improvements and exacerbations of disease activity in relation to the introductions and discontinuations of LDMTX therapy suggest the possible immunosuppresive and anti-inflammatory properties of the drug. Because of a strong correlation between the drug pharmacokinetics and the therapeutic outcomes (pharmacodynamics), it seems to be possible to individualise the LDMTX therapy according to the results of pharmacokinetic/pharmacodynamic analysis. In the case of psoriasis, pharmacokinetic/pharmacodynamic analysis in our local study revealed a highly significant inverse relationship between PASI (expressed as a percent of the initial value) and a steady-state AUC(MTX) (area under the curve of methotrexate plasma concentrations; r(8) = -0.65, p < 0.001). The considerable inter-individual variability and low intra-individual variability in MTX pharmacokinetics, supports a role for therapeutic monitoring and dose individualisation at the start of pharmacotherapy. The results of this study suggest that a steady-state AUC(MTX) value of 700 nmol x h/L and higher are associated with a significantly better success rate of antipsoriatic therapy than lower values. The preliminary results in our follow-up study suggest the statistically higher incidence of unwanted effects depending on maximum plasma concentration of the drug. Moreover, statistically significant correlation was found between the toxic effects and exposure to the drug regarding methotrexate plasma concentrations and intracellular storage in erythrocytes. However, the data are still in the process of being completed and are not yet published.

Department of Pharmacology Charles University Hradec Králové Czech Republic

Zobrazit více v PubMed

Ann Intern Med. 1994 Dec 1;121(11):833-41 PubMed

Eur J Clin Pharmacol. 1998 Feb;53(6):437-44 PubMed

Med Pediatr Oncol. 1982;10(4):401-11 PubMed

Arthritis Rheum. 1986 Jul;29(7):832-5 PubMed

Ann Intern Med. 1987 Sep;107(3):418-9 PubMed

J Pharm Sci. 1989 Feb;78(2):165-71 PubMed

Arthritis Rheum. 1994 Oct;37(10):1492-8 PubMed

J Am Acad Dermatol. 1991 Aug;25(2 Pt 1):306-18 PubMed

Lancet. 1995 Mar 4;345(8949):544-7 PubMed

J Rheumatol. 1998 Jan;25(1):36-43 PubMed

J Rheumatol. 1994 Feb;21(2):203-8 PubMed

Br J Clin Pharmacol. 2002 Aug;54(2):147-56 PubMed

Cancer Res. 1965 Aug;25(7):1018-24 PubMed

Acta Pathol Microbiol Scand A. 1977 Jul;85(4):511-8 PubMed

Acta Derm Venereol. 1986;66(6):515-9 PubMed

Br J Rheumatol. 1998 May;37(5):502-8 PubMed

Clin Pharmacokinet. 1996 Mar;30(3):194-210 PubMed

Arch Dermatol. 1980 Apr;116(4):413-5 PubMed

J Rheumatol. 1997 Nov;24(11):2230-2 PubMed

Acta Med Austriaca. 1988;15(5):140-4 PubMed

J Rheumatol. 1993 Sep;20(9):1573-7 PubMed

Ann Rheum Dis. 1992 Dec;51(12):1330-1 PubMed

J Rheumatol. 1986 Apr;13(2):440-1 PubMed

Arthritis Rheum. 1990 Mar;33(3):330-8 PubMed

Clin Pharmacol Ther. 1991 Nov;50(5 Pt 1):547-56 PubMed

Br J Dermatol. 1994 Feb;130(2):204-10 PubMed

J Rheumatol. 1993 Jun;20(6):950-2 PubMed

Acta Derm Venereol Suppl (Stockh). 1994;186:114-5 PubMed

Br J Clin Pharmacol. 1998 Oct;46(4):369-76 PubMed

Br J Rheumatol. 1995 Nov;34 Suppl 2:20-5 PubMed

Ann Intern Med. 1989 Mar 1;110(5):353-6 PubMed

Arthritis Rheum. 1980 Jan;23(1):119-22 PubMed

Br J Clin Pharmacol. 1993 Apr;35(4):409-12 PubMed

Rheum Dis Clin North Am. 1997 Nov;23(4):739-55 PubMed

Arthritis Rheum. 1992 Feb;35(2):129-37 PubMed

J Rheumatol Suppl. 1990 May;22:16-23 PubMed

J Rheumatol. 1990 Aug;17(8):1008-10 PubMed

Br J Rheumatol. 1997 Nov;36(11):1196-204 PubMed

J Rheumatol. 1995 Jan;22(1):38-40 PubMed

Semin Arthritis Rheum. 1999 Dec;29(3):148-58 PubMed

Osteoporos Int. 1999;10(1):20-5 PubMed

Ann Intern Med. 1997 Sep 1;127(5):356-64 PubMed

Clin Pharmacokinet. 1978 Jan-Feb;3(1):1-13 PubMed

J Immunol. 1996 Jun 1;156(11):4408-14 PubMed

Clin Exp Rheumatol. 1993 Mar-Apr;11 Suppl 8:S97-9 PubMed

Clin Exp Rheumatol. 1995 Jul-Aug;13(4):465-70 PubMed

Arch Dermatol Res. 1998 Dec;290(12):656-60 PubMed

Ann Intern Med. 1989 Aug 1;111(3):261 PubMed

J Rheumatol. 2000 Sep;27(9):2110-4 PubMed

Eur J Clin Pharmacol. 1984;27(5):607-10 PubMed

J Rheumatol. 1990 Dec;17(12):1628-35 PubMed

Clin Nephrol. 1995 Jan;43 Suppl 1:S33-7 PubMed

Br J Dermatol. 1980 Apr;102(4):407-12 PubMed

BioDrugs. 2000 May;13(5):373-9 PubMed

Ann Rheum Dis. 1999 Feb;58(2):79-84 PubMed

Clin Exp Dermatol. 1985 Jan;10(1):30-5 PubMed

Br J Dermatol. 1990 Jan;122(1):1-7 PubMed

Arthritis Rheum. 1992 Jun;35(6):611-4 PubMed

Ann Rheum Dis. 1994 Jul;53(7):434-9 PubMed

J Rheumatol. 1995 Jun;22(6):1009-12 PubMed

J Rheumatol. 1998 Mar;25(3):441-6 PubMed

Br J Clin Pharmacol. 1994 May;37(5):453-6 PubMed

Am J Physiol. 1996 Feb;270(2 Pt 1):C522-9 PubMed

Baillieres Clin Rheumatol. 1990 Dec;4(3):575-93 PubMed

Acta Derm Venereol. 1975;55(4):291-6 PubMed

Am J Gastroenterol. 1997 Dec;92(12):2203-9 PubMed

Rheumatology (Oxford). 2002 Jun;41(6):658-65 PubMed

Rheum Dis Clin North Am. 1997 Nov;23(4):969-80 PubMed

J Rheumatol. 1989 Mar;16(3):313-20 PubMed

J Pediatr. 1998 May;132(5):830-5 PubMed

Acta Derm Venereol. 1992 Sep;72 (5):361-4 PubMed

Ophthalmology. 1999 Jan;106(1):111-8 PubMed

N Engl J Med. 1999 Jan 28;340(4):253-9 PubMed

J Clin Invest. 1998 Jan 15;101(2):295-300 PubMed

Scand J Rheumatol. 1997;26(4):241-6 PubMed

J Rheumatol. 1993 Jul;20(7):1121-5 PubMed

Ann Rheum Dis. 1994 Jul;53(7):475-7 PubMed

Arthritis Rheum. 1990 Jan;33(1):9-18 PubMed

Semin Arthritis Rheum. 1998 Apr;27(5):277-92 PubMed

Rheumatol Int. 1998;18(2):59-62 PubMed

Ann Rheum Dis. 1997 Feb;56(2):97-102 PubMed

J Rheumatol. 1993 Nov;20(11):1845-9 PubMed

Drugs. 1994 Jan;47(1):25-50 PubMed

J Immunol. 1996 May 1;156(9):3435-42 PubMed

Arthritis Rheum. 1993 Jun;36(6):795-803 PubMed

Ther Drug Monit. 1996 Apr;18(2):128-34 PubMed

Br J Rheumatol. 1995 May;34(5):421-8 PubMed

Arthritis Rheum. 1990 Jan;33(1):91-4 PubMed

Clin Exp Dermatol. 1985 May;10 (3):194-200 PubMed

J Rheumatol. 1988 Sep;15(9):1356-60 PubMed

Arthritis Rheum. 1994 Dec;37(12):1770-3 PubMed

Oncol Res. 1997;9(5):259-63 PubMed

Eur J Clin Pharmacol. 1984;26(1):121-4 PubMed

Clin Exp Dermatol. 1990 Sep;15(5):358-60 PubMed

Arthritis Rheum. 1989 Jun;32(6):677-81 PubMed

Lancet. 1995 Oct 21;346(8982):1070-1 PubMed

J Rheumatol. 1991 Apr;18(4):609-10 PubMed

J Clin Invest. 1998 Jul 15;102(2):322-8 PubMed

Eur J Clin Pharmacol. 1996;49(4):285-92 PubMed

Arthritis Rheum. 1992 Feb;35(2):138-45 PubMed

J Natl Cancer Inst. 1966 Aug;37(2):233-45 PubMed

Ther Drug Monit. 1994 Dec;16(6):560-3 PubMed

J Rheumatol. 1994 Jun;21(6):1170-2 PubMed

The effect of folic acid supplementation on the pharmacokinetics and pharmacodynamics of oral methotrexate during the remission-induction period of treatment for moderate-to-severe plaque psoriasis