Pharmacokinetic change in renal failure

Absorption
吸收下降（most clinical non-significant)。
cause by: 腹瀉、嘔吐、soggy gut

Metabolism

• vitamin D

轉換25-hydroxycholecalciferol到1,25-dihydroxycholescalciferol（active form of vitD）的酵素因腎功能差而運作差，故腎衰竭只能補充：

• 1-hydroxycholecalciferol (alfacalcidol)  or
• 1,25-dihydroxycholecalciferol (calcitriol)

• insulin

 在腎臟代謝。所以DM病人AKI通常要調降胰島素量。

Distribution

影響：

• dehydration or oedema 通常只會在Vd<50L的藥物才會有顯著差異
• plasma protein binding

Excretion

Loading dose (mg) = target concentration (mg/L) x volume of distribution (L)

In renal impairment,

Dosing rate in renal failure(DRrf) = normal dosing rate x [ (1-Feu) + (Feu x RF) ]
Feu=fraction of drug normally excreted unchanged in urine
RF=extent of normal impairment (p't CrCl/ideal CrCl)

e.g. if RF=0.2 and Feu=0.5, DRrf=60% of normal


腎毒性

結論：腎功能差的藥物選擇，最好選：

• <25%由腎臟排除 （excreted unchanged in the urine）
• 不會受到身體體液不平衡影響 fluid balance
• unaffected by protein-binding changes
• wide therapeutic margin
• 沒有nephrotoxic問題