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This article evaluates the relationship between the pharmacokinetics of methotrexate (MTX), its efficacy in the treatment of rheumatoid arthritis (RA), and serum folic acid (FA) levels. The pharmacokinetics of MTX was studied in 29 patients with RA treated with low-dose MTX. The weekly dose of MTX was given orally at 2-4 mg every 12 h over a period of 24-36 h. Blood samples were taken 4 h after the first administration in any given week. A Bayesian method was used to estimate individual MTX pharmacokinetic variables. We then investigated the efficacy of MTX and the serum FA levels in these patients. We examined C-reactive protein levels (CRP) and the erythrocyte sedimentation rate (ESR), and analyzed the values obtained before and after MTX treatment in order to evaluate the efficacy of the MTX treatment. The degree of improvement in CRP and ESR was significantly correlated with the length of time the MTX concentration-time curve remained above 0.02 microM in one week. Furthermore, the degree of improvement in CRP was also significantly correlated with the area under the concentration-time curve (AUC) for MTX. These results suggest that serum MTX measurements could be useful in determining individual patient regimens.

This article evaluates the relationship between the pharmacokinetics of methotrexate (MTX), its efficacy in the treatment of rheumatoid arthritis (RA), and serum folic acid (FA) levels. The pharmacokinetics of MTX was studied in 29 patients with RA treated with low-dose MTX. The weekly dose of MTX was given orally at 2-4 mg every 12 h over a period of 24-36 h. Blood samples were taken 4 h after the first administration in any given week. A Bayesian method was used to estimate individual MTX pharmacokinetic variables. We then investigated the efficacy of MTX and the serum FA levels in these patients. We examined C-reactive protein levels (CRP) and the erythrocyte sedimentation rate (ESR), and analyzed the values obtained before and after MTX treatment in order to evaluate the efficacy of the MTX treatment. The degree of improvement in CRP and ESR was significantly correlated with the length of time the MTX concentration-time curve remained above 0.02 microM in one week. Furthermore, the degree of improvement in CRP was also significantly correlated with the area under the concentration-time curve (AUC) for MTX. These results suggest that serum MTX measurements could be useful in determining individual patient regimens.

To establish guidelines for avoiding the side eŠects of mycophenolate mofetil (MMF) in renal transplant recipients with tacrolimus (TAC)-based immunosuppression, the relationship between the daily dose of MMF and the occurrence of side eŠects was analyzed in this study. The frequency of side eŠects was investigated retrospectively in 28 renal transplant recipients treated with immunosuppression (men 14 : women 14, age: 33.0 ± 12.4 years, weight: 50.9 ± 10.7 kg). Cytomegalovirus (CMV) infection and diarrhea were the most frequent side eŠects in the early transplant phase (from transplantation to 3-month biopsy) in the recipients. In 18 recipients, excluding the recipients with risk factors for CMV infection (ABO-incompatible transplantation, donor (＋)/recipient (-) CMV serostatus, etc.), no signiˆcant correlation was shown between the daily dose of MMF and the occurrence of CMV infection in the two-sample t-test. On the other hand, the daily dose in the diarrhea group (33.2 ± 4.3 mg/kg/day, n ＝ 5) was signiˆcantly higher than that in the no-diarrhea group at 30 days (28.4 ± 3.7 mg/kg/day, n ＝ 23, p ＜ 0.05) and 90 days (25.7 ± 4.4 mg/kg/day, n ＝ 21, p ＜ 0.005) after transplantation, respectively. The receiver-operating characteristic (ROC) curve also revealed that the risk of diarrhea increased with a daily MMF dose higher than 30 mg/kg/day. In conclusion, to decrease the risk of diarrhea in the early transplant phase in renal transplant recipients with TAC-based immunosuppression, the daily dose of MMF should not be more than 30 mg/kg/day.

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