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514
17
総論 Appendix 515
516
1.分布容積 517
518
519 図1. 分布容積 520
薬物 Bは 薬物 Aと比較し分布容積が大きく、同用量投与しても血漿中521
濃度は低値となる。同じ薬剤でも患者病態の変化(熱傷、敗血症など)522
により分布容積が大きくなれば(3rd space の広がり)、血漿中濃度は予523
想を下回る 524
525
2.定常状態、クリアランス 526
18
527
図2.定常状態前と定常状態での薬物の投与速度と消失速度の関係.初期は528
一定の維持量を投与しても、生体内分布容積が満たされるまでは投与速度529
(Inの速度)に比較し消失速度(Out の速度)が低値で、その差が体内に蓄530
積される。分布容積が満たされた定常状態になれば in と Outの速度が等し531
くなり、蓄積はなくなり一定の濃度域が維持される。 532
Inの速度:1日維持総投与量を平均した 1時間当たりの投与量。 533
Outの速度:血漿中薬物濃度(ボックス内濃度)とクリアランス(ボックス534
のサイクル)により規定 535
クリアランス:薬物を含んだボックスが運び出され、薬物を廃棄し戻ってく536
るサイクル。宿主状態が変わらなければ一定。 537
Rowland M, Tozer TN. Therapeutic regimens. In: Rowland M, Tozer TN 538
editors. Clinical pharmacokinetics and pharmacodynamics. Concepts 539
and allocations, Fourth edition. Philadelphia: Wolters 540
Kluwer/Lippincott Williams & Wilkins; 2011. P. 245-329. 改変 541
542
3. 臨床成績と相関する PK-PDパラメーター 543
腎機能低下患者に対してアミノグリコシド系薬を使用する場合、1 回投与544
19
量を減量する投与設計を選択すればピーク値は低下し、通常の目標濃度に達545
しないが、臨床的、細菌学的効果に関しては AUCなどの他のパラメーターの546
関与も考慮することができる。小児は成人と薬物動態が異なるため、必ずし547
も本文表 1に示す測定 TDM項目における目標値と一致しない。また VCMを使548
用する場合、同じ 1日投与量であっても投与回数を 2回から 3回に増やすこ549
とにより高いトラフ値が得られるが、AUC は変化せず、臨床的、細菌学的効550
果は変わらない 551
552
4. Area under the plasma concentration time curve (AUC) 553
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シドが共存していると、交差反応を認め定量値が偽高値となることがある 62。 218 b. 検体中に高濃度の β ラクタム系薬が共存しているとアミノグリコシド系薬219
が分解するため、採血後直ちに測定するか冷凍保存する 50,63,64。 220 221
222
8
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