Explaining the acetaminophen–ibuprofen analgesic interaction using a response surface model

Abstract

This drug interaction modeling example is useful to explain combination therapy nuances and impacts on study design. Differences in effect between single drug therapy and combination therapy should be sought at lower doses and beyond the immediate postoperative period. Combination therapy may prolong the duration of analgesia. The maximum effect (E(MAX) ) limits the early additional analgesic gain from combination therapy beyond commonly used doses.

Considerations when using pharmacokinetic/pharmacodynamic modeling to determine the effectiveness of simple analgesics in children

“…Hormones possibly have influence on the higher levels of pain and decreased pain threshold experienced by women because these differences are less Data taken from [69].…”

“…A constant hazard with pain score as a time varying covariate was used. The hazard of dropping out was increased with increased pain score (hazard ratio of 1.35 per unit change in pain) [69].…”

Predicting the Best Fit: A Comparison of Response Surface Models for Midazolam and Alfentanil Sedation in Procedures With Varying Stimulation

“…Steepness (γ) was a function of θ, as shown in Equation 8. In summary, the Minto model required 6 parameters (C 50alf , C 50mid , β 2 50 ,U , γ mid , γ alf , and β γ ).…”

Randomized comparison between the combination of acetaminophen and ibuprofen and each constituent alone for analgesia following tonsillectomy in children

“…A recent simulation study suggested a prolonged analgesic effect for the combination of acetaminophen and ibuprofen compared with either drug alone. 17 Those authors emphasized the importance of scheduling follow-up evaluations for combination therapy that extend beyond the immediate postoperative period. This may explain the finding of Viitanen et al that superiority of the combination was evident only following discharge from hospital 14 as well as our own result that a requirement for post-discharge rescue medication was eliminated for children receiving the combination.…”

“…17 Larger doses (as used in this study) result in concentrations that correspond to the upper portion of the response curve, meaning that the maximal analgesic effect is approached for both drugs, and the difference between the single and combined therapies becomes less evident. This may explain the negative result in our comparison.…”