ε1 (%)−41.7–1451.36–2.410.278–0.846−38.3–1231.38–2.140.408–0.796−262–47144.9–85.40.367–0.9540.199–0.841−258–38744.4–76.80.196–0.8780.455–0.811−15.6–11217.4–63.6068.834.3−29.8–90.915.9–50.1−11.0–97.130.1–85.2024.253.8−NA–38.031.2–73.2AC000000000550000000000D0000000 )Lm/)gLnm(/gn()Lm/)gLnm(/gn()Lm/)gLnm(/gn()Lm/)gLnm(/gn()Lm/)gLnm(/gn()Lm/)gLnm(/gn()Lm/)gLnm(/gn()Lm/)gLnm(/gn()detc)edrerotcCernrooCitcnidoeitrcPi(denroPi(tanvoreitsabvOresbO)detc)edrerotcCernrooCitcnidoeitrcPi(denroPi(tanvoreitsabvOresbO)detc)edrerotcCernrooCitcnidoeitrcPi(dernPo(itanvoreitsabvOresbO)detc)edrerotcCernrooCitcnidoeitrcPi(dernPo(itanvoreitsabvOresbO)detc)edrerotcCernrooCitcnidoeitrcPi(denroPi(tanvoreitsabvOresbO)detc)edrerotcCernrooCitcnidoeitrcPi(denroPi(tanvoreitsabvOres20bO20)detc)edrerotcCernrooCitcnidoeitrcPi(denroPi(tanvoreitsabvOresbO)detc)edrerotcCernrooCitcnidoeitrcPi(denroPi(tanvoreitsabvOresbO(A)(A)(C)(C)(A)(A)(C)(C)(B)(B)(B)(B)(D)(D)(D)(D)Final modelPopulation mean95% CI0.84 FIX80.61.760.602−0.400 −0.542– −0.258 −0.397 −0.544– −0.1460 FIX67.637.233.328.3–37.7TadalafilBootstrap (n=2000)Bootstrap median95% CI0.8476.21.790.58332.727.0–39.8Final modelPopulation mean0 FIX25.556.358.551.8–64.5visual predictive checksSildenafilBootstrap (n=2000)Bootstrap median95%CI95% CI4.5132260.10.6370.53957.951.0–64.2表 2 Sildenafil および Tadalafil 最終モデルにおける母集団薬物動態パラメータおよびブートストラップ解析結果（PDE-5 阻害薬）Pharmacokinetic parameterKa (h-1)4.51 FIX322Vd/F (L)CL/F (L/h)60.6Effect of BW 0.537Effect of BOS0.633Effect of SPIInter-individual variability (%)KaVd/FCL/FResidual errorNA, not applicable; BW, body weight; Ka, absorption rate constant; BOS, concomitant use of bosentan; SPI, concomitant use of spironolactone; Vd/F, apparent volume of distribution; CL/F, apparent total clearance; CI, confidence interval.Sildenafil model: CL/Fpop = 60.6 × (BW / BWmedian)0.537 × (1 + 0.633)BosentanTadalafil model: CL/Fpop = 1.76 × (BW / BWmedian)0.602 × (1 − 0.400)SpironolactoneCLpop, predicted population mean of CL/F; Bosentan, indicator variable for concomitant bosentan; BW, body weight; Spironolactone, indicator variable for concomitant spironolactone図 2 Sildenafil（A）、Tadalafil（B）、Bosentan（C）、および Ambrisentan（D）の最終モデルにおける Prediction-corrected 円は実測値を表す。実線は実測データの 50 パーセンタイル値を示し、破線は 2.5 および 97.5 パーセンタイル値を示す。塗りつぶされた領域は、予測値の 2.5、50、および 97.5 パーセンタイルに対応する 95% 信頼区間を示し、中央の帯（赤）は中央値、上下の帯（青）はそれぞれ 2.5 および 97.5 パーセンタイルに対応する。1501501501501001001001005050505055Time after dose (h)Time after dose (h)55Time after dose (h)Time after dose (h)500050005000400050004000400030004000300030002000300020002000100020001000100001000010151010151001051510201525Time after dose (h)Time after dose (h)51510201525010Time after dose (h)Time after dose (h)B1500150015001500100010001000100050050050050015100Time after dose (h)10Time after dose (h)151500150015001500100010001000500100050050050025010Time after dose (h)10Time after dose (h)2520203010Time after dose (h)10Time after dose (h)30203020303020302010Time after dose (h)10Time after dose (h)30202030100
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