Pharmacokinetics of paracetamol (Perfalgan®) following different infusion protocols in a porcine model
Sheikh, Sohail Ahmed
Introduction:
Perfalgan® is a newly developed; direct inject able form of paracetamol. The recommended infusion rate for Perfalgan® is 1g over 15 minutes. This recommendation is based on the rationale that paracetamol acts centrally and to achieve an efficacious cerebrospinal fluid (CSF) level of paracetamol a high gradient between plasma and liquor is essential.
Aim of the trial:
Aim of the present investigation was to evaluate, whether similar efficacious CSF levels of Perfalgan® could be obtained after an infusion rate of 1g over 60 minutes.
Methods:
Experiments were performed in 10 anaesthetized female German domestic pigs. The pigs were randomized either in the group with an infusion rate of 15 minutes (n=5) or 60 minutes (n=5). In the 15-minutes-group plasma and CSF samples were taken 15, 30, 60, 90 120, 150, 180, and 210 minutes after starting the infusion. In the 60-minutes-group plasma samples were taken 60 minutes after starting the infusion and every 30 minutes up to 210 minutes. CSF samples were obtained after 90, 120, 150, 180, and 210 minutes.
Results:
There were no differences between the groups regarding age (15-min-group: 11 - 13 weeks; 60-min-group: 11 - 14 weeks) and body weight (15-min-group: 38.8 – 41.7 kg; 60-min-group: 38.5 – 41.9 kg).
The elimination half-life (t ½ beta) of the drug was found to be longer in 60-minutes-group [(median±SD) 176± 127.62min] as compared to that in 15-min-group [120± 28.72 min]. The clearance (Cl) was lower in the 60-min-group [(median±SD) 94.9±45.73 ml/l)] as compared to that in the15-min-group [181±67 ml/l]. The values of maximum plasma concentration (C max) were (median±SD) 35.1± 17.48 in the 15-min-group and 37± 7.42 mg/l in the 60-min-group. The volumes of distribution at steady state (Vss) were (median+/-SD) 31.5±8.46 l in 15-min-group and 25.2±8.18 l in the 60-min-group.
Our results indicate that plasma levels are higher in the 60-minutes-group as compared to that in 15-minutes-group in the time interval between 60 and 180 minutes after starting the infusion. In the time interval between 90 and 210 minutes CSF levels were similar in both groups.
Conclusion:
The intravenous infusion of 1g paracetamol over a period of 60 minutes instead of recommended duration of 15 minutes results in higher plasma and similar CSF concentrations. Pharmacokinetics suggests that, the analgesic effect of paracetamol for an infusion over 60 minutes is superior to the recommended infusion over 15 minutes. The infusion protocol for patients´ treatment should be scrutinized in randomized clinical trial
Philipps-Universität Marburg
Medical sciences Medicine
https://doi.org/10.17192/z2008.0710
urn:nbn:de:hebis:04-z2008-07102
opus:2176
Paracetamol
Pharmacokinetics of paracetamol (Perfalgan®) following different infusion protocols in a porcine model
Introduction:
Perfalgan® is a newly developed; direct inject able form of paracetamol. The recommended infusion rate for Perfalgan® is 1g over 15 minutes. This recommendation is based on the rationale that paracetamol acts centrally and to achieve an efficacious cerebrospinal fluid (CSF) level of paracetamol a high gradient between plasma and liquor is essential.
Aim of the trial:
Aim of the present investigation was to evaluate, whether similar efficacious CSF levels of Perfalgan® could be obtained after an infusion rate of 1g over 60 minutes.
Methods:
Experiments were performed in 10 anaesthetized female German domestic pigs. The pigs were randomized either in the group with an infusion rate of 15 minutes (n=5) or 60 minutes (n=5). In the 15-minutes-group plasma and CSF samples were taken 15, 30, 60, 90 120, 150, 180, and 210 minutes after starting the infusion. In the 60-minutes-group plasma samples were taken 60 minutes after starting the infusion and every 30 minutes up to 210 minutes. CSF samples were obtained after 90, 120, 150, 180, and 210 minutes.
Results:
There were no differences between the groups regarding age (15-min-group: 11 - 13 weeks; 60-min-group: 11 - 14 weeks) and body weight (15-min-group: 38.8 – 41.7 kg; 60-min-group: 38.5 – 41.9 kg).
The elimination half-life (t ½ beta) of the drug was found to be longer in 60-minutes-group [(median±SD) 176± 127.62min] as compared to that in 15-min-group [120± 28.72 min]. The clearance (Cl) was lower in the 60-min-group [(median±SD) 94.9±45.73 ml/l)] as compared to that in the15-min-group [181±67 ml/l]. The values of maximum plasma concentration (C max) were (median±SD) 35.1± 17.48 in the 15-min-group and 37± 7.42 mg/l in the 60-min-group. The volumes of distribution at steady state (Vss) were (median+/-SD) 31.5±8.46 l in 15-min-group and 25.2±8.18 l in the 60-min-group.
Our results indicate that plasma levels are higher in the 60-minutes-group as compared to that in 15-minutes-group in the time interval between 60 and 180 minutes after starting the infusion. In the time interval between 90 and 210 minutes CSF levels were similar in both groups.
Conclusion:
The intravenous infusion of 1g paracetamol over a period of 60 minutes instead of recommended duration of 15 minutes results in higher plasma and similar CSF concentrations. Pharmacokinetics suggests that, the analgesic effect of paracetamol for an infusion over 60 minutes is superior to the recommended infusion over 15 minutes. The infusion protocol for patients´ treatment should be scrutinized in randomized clinical trial
Publikationsserver der Universitätsbibliothek Marburg
Universitätsbibliothek Marburg
Medical sciences Medicine
Medizin
https://archiv.ub.uni-marburg.de/diss/z2008/0710/cover.png
Medizin
2008-11-24
Pharmakokinetik
Sheikh, Sohail Ahmed
Sheikh
Sohail Ahmed
https://doi.org/10.17192/z2008.0710
doctoralThesis
urn:nbn:de:hebis:04-z2008-07102
Pharmacokinetik von Paracetamol (Perfalgan®)im porcinen Tiermodell nach unterschiedlichen Infusionsprotokollen
Acetaminiphen
ths
Prof. Dr.
Wulf
Hinnerk
Wulf, Hinnerk (Prof. Dr.)
Paracetamol
2008-10-06
opus:2176
Pharnmaockinetics
Medizin
Pharmakokinetik
Philipps-Universität Marburg
2008
English
55
application/pdf
Einleitung:
Perfalgan® ist die intravenös applizierbare Form von Paracetamol. Die empfohlene Infusionsrate beträgt 1g über 15 Minuten. Diese Empfehlung basiert aus dem Rational, dass Paracetamol zentral wirkt und ein hoher Gradient zwischen Plasma und Liquor notwendig ist, um eine ausreichende Konzentration im Liquor zu erreichen.
Ziel der Studie:
Ziel der Studie war es, zu untersuchen, ob vergleichbare Konzentrationen im Liquor nach intravenöser Gabe von 1g Paracetamol über 60 Minuten zu beobachten sind.
Methode:
Die Untersuchung wurde an zehn weiblichen Hausschweinen in Allgemeinanästhesie durchgeführt. Die Versuchstiere wurden randomisiert entweder der 15-Minuten-Gruppe (n= 5) oder der 60-Minuten-Gruppe (n= 5) zugeteilt. In der 15-Minuten-Gruppe wurden die Plasma- und Liquorproben 15, 30, 60, 90 120, 150, 180 und 210 Minuten nach Beginn der Infusion entnommen. In der 60-Minuten-Gruppe wurden die Plasmaproben 60, 90 120, 150, 180 und 210 Minuten nach Beginn der Infusion entnommen. Die Liquorproben wurden nach 90, 120, 150, 180 und 210 Minuten gewonnen.
Ergebnisse:
Zwischen den Gruppen zeigten sich keine Unterschiede hinsichtlich Alter (15-Minuten-Gruppe: 11 - 13 Wochen; 60-Minuten-Gruppe: 11 - 14 Wochen)und Körpergewicht (15-Minuten-Gruppe: 38.8 – 41.7 kg; 60-Minuten-Gruppe: 38.5 – 41.9 kg).
Die Eliminationshalbwertszeit (t ½ beta) von Paracetamol war in der 60-Minuten-Gruppe [(Median±SD) 176± 127.62min] vergleichsweise länger als in der 15-Minuten-Gruppe [120± 28.72 min]. Die Clearance (Cl) war niedriger in der 60-Minuten-Gruppe [94.9±45.73 ml/l] als in der 15-Minuten-Gruppe [181±67 ml/l]. Die Resultate für die maximale Plasmakonzentration (C max) waren 35.1± 17.48 in 15-Minuten-Gruppe und 37± 7.42 mg/l in der 60-Minuten-Gruppe. Die Verteilungsvolumina im Steady state (Vss) waren 31.5±8.46 l (15-Minuten-Gruppe)und 25.2±8.18 l (60-Minuten-Gruppe).
Die Ergenisse der Plasmakonzentrationen waren wischen 90 und 180 Minuten nach Infusionsbeginn in der 60-Minuten-Gruppe höher als in der 15-Minuten-Gruppe. Für das Zeitintervall zwischen 90 und 210 Minuten waren die Liquorkonzentration vergleichbar.
Schlussfolgerung:
Die intravenöse Applikation von 1g Paracetamol über 60 Minuten zeigt im Vergleich zur Infusion über 15 Minuten höhere Plasmaspiegel und vergleichbare Liquorkonzentrationen. Die Ergebnisse der Pharmacokinetik weisen auf eine Verbesserung des analgetischen Effekts hin, wenn Paracetamol über 60 Minuten an Stelle der emppfohlenen 15 Minuten appliziert wird. Zukünftige klinischen Studien sind notwendig, um eine mögliche Verbesserung des analgetischen Effekts zu evaluieren.
2011-08-10
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