Fa?

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Fa?µa??????t??? ??d?f??ß?a? ??????s??

• 1) ?a?e?a e?d?f??ß?a ??????s? (bolus intravenous
  injection)
• ??d?a??e?a?? ??????s? fa?µ????
• Fa?µa??????t??? ?a?????te? p?? ep??e????? t?
  ???µ? ?a? t?? ??tas? t?? ap????f?s??, ?ata??µ??,
  µetaß???sµ?? ?a? ap?????s?? t?? fa?µ????.
• ??t??s? t?? fa?µ???? ?????? st? p??sµa, ???
  a?µat??, a?µa ?a? ???a.
• ?e t?? ta?e?a e?d?f??ß?a ????s? ep?t???????ta?
  ?????? s???e?t??se?? t?? fa?µ???? st? a?µa se
  s??t?µ? ??????? d??st?µa - ta?e?a ??a???
  fa?µa????????? d??s?? ???d???? t?????t?ta?.

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Fa?µa??????t???? ??ad??as?e? Fa?µ????
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?p?µ?????s? t?? ?e??? ap? t? d??e??
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Fa?µa??????t??? ?a?e?a? ??d?f??ß?a? ??????s??
(Bolus)

• F?s? ?ata??µ?? s?????? d?a??e? µ???? ???????
  d??st?µa - t? ????te?? pe??p?? 10 min (??a
  d?aµ???sµa)
• F?s? ap?µ?????s?? ????a fa?µa??????t???
  d?ad??as?a (ß?ad?te?? d?ad??as?a)
• ?s? pe??ss?te?? ?e?? ?p???e? st? d??e?? t?s?
  µe?a??te??? e??a? ? ???µ?? ap?µ?????s?? t?? ap?
  t? d??e??
• dA/dt -k.A (1)
• ?p?? ? ??s?t?ta t?? ?e??? st? d??e??
• dA/dt ???µ?? µetaß???? t?? p?s?t?ta? t?? ?e???
  st? d??e??
• k Sta?e?? ta??t?ta? ap?µ?????s?? t?? ?e???
  (sta?e?? a?a????a? a???t???)

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Fa?µa??????t??? ?a?e?a? ??d?f??ß?a? ??????s??
(Bolus)

• ???????????ta? t?? p??????µe?? s??s? pa?????µe
• A A0.e-kt (2)
• G?a t 0 t?te e-kt 1 ?a? A A0
• ? ???µ?? µetaß???? t?? ?e??? st? d??e?? e??a?
  a??????? t?? p?s?t?ta? t?? ?e??? st? d??e??
• St?? pe??pt?s? t?? ta?e?a? e?d?f??ß?a? ????s??
  ?s????? ta ?d?a (p???p??es? p??? ???????
  ?ata??µ?)
• A D.e-kt (3)
• ?p?? ? ??s?t?ta t?? fa?µ???? st? s?µa ??a µ?a
  ded?µ??? ??????? st??µ?
• D ?????? p?s?t?ta (d?s?) t?? fa?µ????
• k Sta?e?? ta??t?ta? ap?µ?????s?? t?? fa?µ????

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Fa?µa??????t??? ?a?e?a? ??d?f??ß?a? ??????s??
(Bolus)

• ???a???µ??ta? t?? p??????µe?? s??s? pa?????µe
• lnA lnD kt
• ?µ????a???µ??? ?a?t? (e??e?a ??aµµ?
  fa?µa??????t??? p??t?? t??e?? linear kinetics)
• ????t??? µ?de????? t??e?? (???esµ??) µ? ??aµµ???
  fa?µa??????t??? non-linear kinetics
• ???s? e??e?a?, slope (lnC1-lnC2)/(t1-t2)
• ???? ?a??? t??p?? ??a t?? ?p?????sµ? t?? ???s??
  (a???t??? ? ???s?)
• ??a????ta? t? s??s? A A0.e-kt µe t?? ????
  ?ata??µ?? (V) pa?????µe t? s??s?
• A/V C C0.e-kt
• ?p?? C0 S?????t??s? t?? fa?µ???? ??a ????? t
  0

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Fa?µa??????t??? ?a?e?a? ??d?f??ß?a? ??????s??
(Bolus)

• G?a A D/2 (µ?s? t?? d?s??) pa?????µe A/D
  1/2 ekt1/2
• ln1/2 -kt1/2 ?a? ln2 kt1/2
• t1/2 0.693/k (?????? ?µ?se?a? ????, half-life)
• ? ?????? ?µ?se?a? ???? e??a? a?e???t?t?? ap? t?
  d?s? ?a? e??a? ?a?a?t???st???? ??a ???e f??µa??
• ?????? f?s? ?ata??µ?? 10 20 min. ? C0
  ?p??????eta? µe ep??tas? (extrapolation) t??
  e??e?a? ap?µ?????s??.
• ?p? t? s??s? V D/C0 µp????µe ?a ?p?????s??µe t?
  V (??? p??? a???ß?? µ???d??)
• Fa?µa??????t???? pa??µet???
• t1/2 ?????? ?µ?se?a? ???? Se 5 t1/2 t? 97 t??
  fa?µ???? ap?µa????eta?. k Sta?e?? ta??t?ta?
  ap?µ?????s?? (??????-1)
• k dA/(dt.A)

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Fa?µa??????t??? ?a?e?a? ??d?f??ß?a? ??????s??
(Bolus)

• ? ?????? ?µ?se?a? ???? de? e?a?t?ta? ap? t? d?s?
  ?a? e??a? ?a?a?t???st???? ??a ???e f??µa??
• ?p? t? s??s? A D.e-kt pa?????µe t? s??s?
• A/D e-kt (??s?st? fa?µ???? p?? pa?aµ??e? st?
  s?µa).
• ?? e?f??s??µe t? ????? se ??????? ?µ?se?a? ????,
  t?te pa?????µe t? s??s? n t/t1/2 an? t??
  ?p??a pa?????µe t n.t1/2 ?a? t n.0.693/k
• A/D e-k.0.693.n/k e-0.693n a??? e-0.693 1/2
  
• A/D e-kt (1/2)n
• 50, 75, se 3.3t1/2 90
• dA/dt CL.C k.A k.V.C ?a? CL k.V
• k CL/V ?a? t1/2 0.693V/CL

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Fa?µa??????t??? ?a?e?a? ??d?f??ß?a? ??????s??
(Bolus)
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Fa?µa??????t??? ?a?e?a? ??d?f??ß?a? ??????s??
(Bolus)

• ?? k ?a? ? t1/2 e?a?t??ta? ap? t?? ???a?s? ?a?
  t?? ???? ?ata??µ??
• AUC (Area Under the Curve) ?µßad?? ??t? ap? t??
  ?aµp??? t?? s?????t??s?? t?? fa?µ???? st? p??sµa
  ??????
• ???µ?? ap?µ?????s?? dA/dt CL.C
• dA CL.C.dt ?p?? C.dt ?µßad?? (Area) ??t? ap?
  t?? ?aµp??? C-t.
• G?a p??? µ???? ??????? d??st?µa, dt, pa?at????µe
  ?t? ? p?s?t?ta t?? fa?µ???? p?? ap?µa???????e,
  dA, ?s??ta? µe t? ????µe?? t?? ???a?s??, CL, ep?
  t? eµßad?? ??t? ap? t?? ?aµp??? C-t.
• ???????????ta? t? s??s? dA CL.C.dt pa?????µe t?
  s??s?
• D CL.AUC0-8 ?a? CL D/AUC0-8

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Fa?µa??????t??? ?a?e?a? ??d?f??ß?a? ??????s??
(Bolus)

• ??a? ?a??te??? (p?? a???ß??) t??p?? ??a t??
  ?p?????sµ? t?? CL ?a? t?? V, a?e???t?ta a? ?s??e?
  t? µ???d?aµe??sµat??? p??t?p? (fa?µa??????t???
  p??t?? t??e??, ??aµµ??? fa?µa??????t???)
• ???e? s??se??
• CL k.V
• V CL/k D/(k.AUC0-8) ?a?
• V (1.44D.t1/2)/AUC0-8

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?µßad?? ??t? ap? t?? ?aµp??? C-t (AUC)
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?µßad?? ??t? ap? t?? ?aµp??? C-t (AUC)
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?a??t??? ?????s?
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?p?????sµ?? t?? AUC

• ?a???a? t?? t?ape???? (trapezoidal rule)
• E (t2 t1) x C2 1/2(t2 t1) x (C1 C2)
• ? 1/2(t2 t1) x (C1 C2)
• AUCt1-t2 1/2(C1 C2) x (t2 t1)
• AUC0-8 ?????sµa t?? ep?µ????? t?ape????
• AUCtn-8 Ctn/k ?a? AUC0-8 C0/k (??a ta?e?a
  e?d?f??ß?a ??????s? ta?e?a ?ata??µ?)
• AUC0-8 AUC0-tn Ctn/k
• ????? de??µata ??a a???ß? ?p?????sµ? t?? AUC

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?p?????sµ?? t?? AUC
t (h) C (mg/L) ti1-ti 1/2(C1 C2) (mg/L) AUC (mg/h/L)
0 1 2 3 4 5 6 0 7 10 5 2.5 1.25 0.6 1 1 1 1 1 1 3.5 8.5 7.5 3.75 1.88 0.93 3.5 8.5 7.5 3.75 1.88 0.93 25.96
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?p?????s? t?? Fa?µ???? sta ???a

• G?a f??µa?a p?? ape???????ta? ??µ??? aµet?ß??ta
  sta ???a se s?et??? µe???? p?s?st? (fe ?)
• ??????a s??????? t?? ?????
• S?????? a???µ??? s?????t??s? t?? fa?µ???? sta
  ???a
• ?e???t? p??ß??µata ??? µe???? a???ße?a
  ap?te?esµ?t??
• ???µ?? ap?????s?? dAe/dt CLR.C ?a? C A/V
• dAe/dt (CLR.A)/V ?a? k CL/V, ke CLR/V
• dAe/dt ke.V.C ke.A ke.D.e-kt
• fe Ae(8)/D
• ?p?? fe ??s?st? t?? fa?µ???? p?? ape?????eta?
  ??µ??? a??paf? sta ???a (t?µ?? fe ap? 0 ??? 1)
• Ae(8) ?????st??? p?s?t?ta t?? fa?µ???? sta ???a
  

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?p?????s? t?? Fa?µ???? sta ???a
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?p?????s? t?? Fa?µ???? sta ???a
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?p?????s? t?? Fa?µ???? sta ???a

• fe (dAe/dt)/(dA/dt) CLR/ CL (ke.V)/(k.V)
  ke/k
• dAe/dt ke.D.e-kt ap? t?? ?p??a µe ????????s?
  pa?????µe
• Ae(t) (ke.D)/k.1- e-kt fe.D.1- e-kt
• fe.D - Ae(t) fe.D.e-kt
• ?p?? fe.D - Ae(t) ARE ??s?t?ta t?? fa?µ????
  p?? p???e?ta? ?a ape?????e? sta ???a.
  ???a???µ??ta? pa?????µe
• lnARE ln(fe.D) - kt
• S????????ta? ????µe 3 s??se?? ap? t?? ?p??e?
  µp????µe ?a ?p????????µe t? k
• 1) lnC ln C0 kt
• 2) ln(Rate) ln(ke.D) kt
• 3) ln(ARE) ln(fe.D) - kt

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?p?????s? t?? Fa?µ???? sta ???a
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?p?????s? t?? Fa?µ???? sta ???a

• G?a t?? ?p?????sµ? t?? Ae(8) apa?te?ta? ? s??????
  t?? ????? ??a p??? ap? 5 ??????? ?µ?se?a? ????.
• ?p? ta ded?µ??a t?? ????? µp????µe ?a
  ?p?????s??µe ta k, ke ?a? fe. ?µ?? ??a t??
  ?p?????sµ? t?? CL ?a? t?? V apa?t???ta? ded?µ??a
  t?? p??sµat??