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PHARMACOKINETIC DESCRIPTION OF PLASMA LEVELS OF DRUGS - INTRAVENOUS INFUSION |
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Used for maintenance of plasma levels and therapeutic effect.
Avoids fluctuations in plasma levels associated with repeated boluses.
Provides precise and ready control of administration rate, plasma levels, and effect.
Eg. Morphine/Pethidine; Lignocaine; Nitroglycerine
Time to reach steady-state or plateau level:
Sole factor determining time taken is t½. Takes ~ 4-5 half-lives.
Bolus dose and infusion.
Plasma concentration at plateau:
/ ClRate in = Rate out
R
= Cl x C
= R
Example 1:
AM, a 55 year old 70kg male, was admitted to ICU with a diagnosis of heart failure, probably myocardial infarction, and premature ventricular contractions. What loading dose of Lignocaine should be administered to achieve an immediate response?
(Data: Vd of Lignocaine in heart failure is 0.3L/kg; therapeutic levels are 1-5mg/L).
| Loading dose | = | Vd x C |
| = | 0.3 X 70 X 3mg | |
| = | 63mg or approx. 60mg given slowly by IV push. |
C = Infusion
rate
Therefore,
infusion rate = C X Cl
Example 2:
What maintenance infusion rate of Lignocaine should be administered to patient AM (Example 1) to achieve a steady state plasma concentration of 2mg/L?
(Data: Lignocaine clearance in heart failure is 6ml/min/kg).
Infusion rate = C = 2 x 0.006 x 70mg/min = 0.84mg/min
Plasma concentration before plateau achieved:
C |
= | C x
fraction of steady - state achieved at time t |
| . | ||
| = | C x (1
- e ) |
Plasma concentration post-infusion:
(a) Steady-state achieved:
C =
C x e (t = time post-infusion)
(b) Before steady-state achieved:
t1 = time
for which infusion ran
t2 = time
since infusion ceased
C
=
C x
(1 - e
) x
(e
)
Intravenous bolus and infusion:
To achieve
"steady-state levels" rapidlyResulting plasma levels are a sum of the bolus and infusion components.
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C |
Co
. e |
C (1 -
e)
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+ |
________________ |
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bolus |
infusion | |||
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C |
dose |
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________
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. e
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+ |
C (1 -
e)
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Vd |
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