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药代动力学
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药代动力学
12
engines
Loading dose vs maintenance dose
Loading dose vs maintenance dose
LD=Css·Vd/F · 维持MD=Css·CL·τ/F · 瞬时达标
A loading dose reaches the target instantly; maintenance alone takes ~5 half-lives
Multi-dose accumulation & steady state
Multi-dose accumulation & steady state
蓄积比R=1/(1−e^(−kτ)) · 稳态峰谷 · 锯齿曲线
Repeat a dose every τ; concentration saw-tooths up to steady state over ~5 half-lives
Plasma concentration-time curve by route
Plasma concentration-time curve by route
IV弹丸e^(−kt) · 口服Bateman · 恒速输注达Css
IV bolus, oral (Bateman) and constant infusion — the same drug, three input shapes
Volume of distribution Vd
Volume of distribution Vd
Vd=Dose/C0 · 血浆/ECF/全身水/组织结合
Vd = Dose / C₀ · compare against physiological fluid volumes
Area under the curve (AUC)
Area under the curve (AUC)
梯形法AUC · AUC∞=Clast/k · CL=F·Dose/AUC
AUC by the trapezoidal rule · log-linear tail · clearance CL = F·Dose / AUC
Hepatic clearance & extraction ratio
Hepatic clearance & extraction ratio
CL_h=Q·E · 抽提比E · 血流限速vs容量限速
Well-stirred model · E = fu·CL_int / (Q + fu·CL_int) · CL_h = Q·E
Bioavailability F · absolute & relative
Bioavailability F · absolute & relative
F=(AUC口服·剂量IV)/(AUC_IV·剂量口服) · 绝对/相对
F_abs = (AUC_oral · Dose_iv) / (AUC_iv · Dose_oral) · IV is the 100% reference
First-pass metabolism · oral F = Fa·Fg·Fh
First-pass metabolism · oral F = Fa·Fg·Fh
F=Fa·Fg·Fh · 肝抽提1−E · 口服<IV
F = Fa · Fg · (1 − E) · the three survival fractions multiply
Plasma protein binding · free fraction fu
Plasma protein binding · free fraction fu
游离分数fu=1/(1+Ka·P) · 仅游离药有效 · 置换
fu = 1 / (1 + Ka·[P]) · only free drug distributes, acts & clears
Two-compartment PK · bi-exponential disposition
Two-compartment PK · bi-exponential disposition
双指数C=A·e^(−αt)+B·e^(−βt) · 分布相+消除相
C(t) = A·e^(−αt) + B·e^(−βt): a steep distribution phase, then a shallow elimination line
Saturable elimination · Michaelis–Menten PK
Saturable elimination · Michaelis–Menten PK
米氏Vmax·C/(Km+C) · 低浓一级/高浓零级 · 非线性
rate = Vmax·C/(Km+C): first-order when C≪Km, zero-order when C≫Km
Therapeutic window · MEC, MTC & dosing
Therapeutic window · MEC, MTC & dosing
MEC/MTC · Css保持窗内 · 治疗指数MTC/MEC
Keep the saw-tooth between MEC and MTC; therapeutic index = MTC/MEC