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1.  Combined acetaminophen and ibuprofen for pain relief after oral surgery in adults: a randomized controlled trial 
Background
Acetaminophen is often used with a non-steriodal anti-inflammatory drug for acute pain. Hitherto, these drugs have had to be given separately, typically at different time intervals. Maxigesic® tablets combine acetaminophen and ibuprofen in clinically appropriate doses to simplify administration and dosage regimen. We compared this combination with each of the constituent drugs for the relief of pain after extraction of third molar teeth.
Methods
Adults (more than 16 yr) having one or more wisdom teeth removed under general or local anaesthesia were instructed to take two tablets before operation, then two tablets every 6 h for up to 48 h of: (i) a combination of acetaminophen 500 mg and ibuprofen 150 mg per tablet (Maxigesic®); (ii) acetaminophen 500 mg per tablet alone; or (iii) ibuprofen 150 mg per tablet alone. The primary outcome measure was the area under the curve (AUC) of the 100 mm visual analogue scale pain measurements taken for up to 48 h after surgery, divided by time, at rest and on activity. Pharmacokinetic data were collected in a subset of patients.
Results
The mean (sem) time-corrected AUC on rest and activity, respectively, were: combination group 22.3 (3.2) and 28.4 (3.4); acetaminophen group 33.0 (3.1) and 40.4 (3.3); and ibuprofen group 34.8 (3.2) and 40.2 (3.4); P<0.01 for each of the four comparisons of combination vs constituent drug. There was no pharmacokinetic interaction between acetaminophen and ibuprofen administered together.
Conclusions
Maxigesic® tablets provide superior pain relief after oral surgery to acetaminophen or ibuprofen alone.
doi:10.1093/bja/aep338
PMCID: PMC2791549  PMID: 20007794
anaesthesia, dental; analgesia, postoperative; analgesics non-opioid, acetaminophen; analgesics non-opioid, ibuprofen; non-steroidal anti-inflammatory drugs
2.  Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial 
BJA: British Journal of Anaesthesia  2008;101(5):680-689.
Background
Relationships between plasma morphine concentrations and neonatal responses to endotracheal tube (ETT) suctioning are unknown in preterm neonates.
Methods
Ventilated preterm neonates (n=898) from 16 centres were randomly assigned to placebo (n=449) or morphine (n=449). After an i.v. loading dose (100 µg kg−1), morphine infusions [23–26 weeks postmenstrual age (PMA) 10 µg kg−1 h−1; 27–29 weeks 20 µg kg−1 h−1; and 30–32 weeks 30 µg kg−1 h−1] were established for a maximum of 14 days. Open-label morphine (20–100 µg kg−1) was given for pain or agitation. Morphine assay and neonatal response to ETT suctioning was measured at 20–28 and 70–76 h after starting the drug infusion and at 10–14 h after discontinuation of the study drug. The concentration–effect response was investigated using non-linear mixed effects models.
Results
A total of 5119 data points (1598 measured morphine concentrations and 3521 effect measures) were available from 875 neonates for analysis. Clearance was 50% that of the mature value at 54.2 weeks PMA (CLmat50) and increased from 2.05 litre h−1 70 kg−1 at 24 weeks PMA to 6.04 litre h−1 70 kg−1 at 32 weeks PMA. The volume of distribution in preterm neonates was 190 litre 70 kg−1 (CV 51%) and did not change with age. There was no relationship between morphine concentrations (range 0–440 µg litre−1) and heart rate changes associated with ETT suctioning or with the Premature Infant Pain Profile.
Conclusions
A sigmoid curve describing maturation of morphine clearance is moved to the right in preterm neonates and volume of distribution is increased compared with term neonates. Morphine does not alter the neonatal response to ETT suctioning.
doi:10.1093/bja/aen248
PMCID: PMC2733178  PMID: 18723857
anaesthesia, paediatric; anaesthetic–analgesic regimens; analgesics opioid, morphine; model, pharmacodynamic; model, pharmacokinetic

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