2008
DOI: 10.1136/adc.2007.126896
|View full text |Cite
|
Sign up to set email alerts
|

Paracetamol (acetaminophen) pharmacodynamics: interpreting the plasma concentration

Abstract: Interpretation of analgesic and antipyretic responses documented after paracetamol administration is confused because response is not directly related to concentration in the blood, but rather to an effect compartment. The effect compartment does not have real measurable concentrations, but concentrations equate approximately to those observed in the cerebrospinal fluid. A time delay exists before drug reaches the effect compartment, and the equilibration half-time between the central and effect compartment is… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

1
80
0

Year Published

2008
2008
2021
2021

Publication Types

Select...
6
4

Relationship

0
10

Authors

Journals

citations
Cited by 95 publications
(83 citation statements)
references
References 35 publications
(43 reference statements)
1
80
0
Order By: Relevance
“…In analyzing the drug effects using a compartmental PK model, the transition of the drug from the central compartment to the effect site should be taken into account as the drug concentration would enhance the drug effect. The cerebrospinal fluid (CSF) concentrations can be equated to be the effect site concentrations [14] because the time course of acetaminophen concentration in CSF correlates with the analgesic and antifebrile effect of the drug [15]. Because acetaminophen is thought to penetrate the blood−brain barrier by passive diffusion due to a concentration gradient, larger peak concentrations after i.v.…”
Section: Discussionmentioning
confidence: 99%
“…In analyzing the drug effects using a compartmental PK model, the transition of the drug from the central compartment to the effect site should be taken into account as the drug concentration would enhance the drug effect. The cerebrospinal fluid (CSF) concentrations can be equated to be the effect site concentrations [14] because the time course of acetaminophen concentration in CSF correlates with the analgesic and antifebrile effect of the drug [15]. Because acetaminophen is thought to penetrate the blood−brain barrier by passive diffusion due to a concentration gradient, larger peak concentrations after i.v.…”
Section: Discussionmentioning
confidence: 99%
“…Following a 1 g dose, participant blood levels may fall below this laboratory cut-off level in as little as 3 h (given a paracetamol half-life of 2 h and a peak plasma concentration 1 h after administration of 80 μmol/L38). The use of this laboratory cut-off for paracetamol levels meant that it was not possible to investigate medication compliance through this method.…”
Section: Discussionmentioning
confidence: 99%
“…Consequently, a loading dose of 20 mg/kg to adapt for the higher distribution volume, followed by a 6-hourly 10 mg/kg dose to adapt for the lower clearance in neonates was suggested 33. In contrast to these pharmacokinetic estimates, there are still no robust data to disentangle paracetamol pharmacokinetics and pharmacodynamics in newborns 34. Data are limited to haemodynamics, hepatic tolerance and body temperature dynamics 3537.…”
Section: Common and Emerging Analgosedatives In Neonatesmentioning
confidence: 99%