メトトレキサート2mg錠（メトレート^®錠2mg）経口投与後の関節リウマチ患者における薬物体内動態シミュレーション ―母集団薬物動態解析により得られた薬物動態パラメーターを用いた解析―

抄録

    The serum concentration of methotrexate (MTX) after oral administration of MTX was simulated using the following pharmacokinetics parameters (Ka＝0.503(h⁻¹), Ke＝1.391(h⁻¹), K₁₂＝1.118(h⁻¹), K₂₁＝0.1521(h⁻¹), α＝2.5791(h⁻¹), β＝0.082034 (h⁻¹)) which were calculated by population pharmacokinetics parameters in a previous paper (Yukawa, E., et al., Journal of Clinical Pharmacy and Therapeutics, 32: 573-578, 2007). These population pharmacokinetic parameters were investigated after low-dose MTX (Metolate^® tablets 2 mg) in rheumatoid arthritis patients and healthy male volunteers. The simulation of MTX serum concentration was performed by three classes according to the weight of patients as 45, 60 and 75 kg. The Cmax was simulated 240 ng/mL at 1 hour after administration of 4 mg of MTX to the patient (45 kg). The simulation showed no accumulation of MTX after multiple dosing, and the serum concentrations of MTX measured after multiple administrations at a dose of 4 mg, 2 mg and 2 mg every 12 hours to patients (57-65 kg) were very close to the simulation results for the same dose to patients weighing 60 kg. We could conclude our simulation MTX was useful to estimate the serum profiles of MTX in individual patients and might permit selection of an appropriate dosage to achieve target MTX concentrations, thus enabling the clinician to achieve the desired therapeutic effect in Japanese patients.