Onset of analgesia and analgesic efficacy of tramadol/acetaminophen and codeine/acetaminophen/ibuprofen in acute postoperative pain: a single-center, single-dose, randomized, active-controlled, parallel-group study in a dental surgery pain model.
BACKGROUND
The combination of tramadol and acetaminophen has demonstrated good efficacy in various clinical pain models. However, there is a need for comparisons of the onset of analgesia and other measures of analgesic efficacy with this combination and other strong combination analgesics for the management of acute pain.


OBJECTIVE
The goal of this study was to compare the time to onset of analgesia and other measures of analgesic efficacy with tramadol/acetaminophen 75/650 mg (Tr/Ac) and codeine/acetaminophen/ibuprofen 20/500/400 mg (Co/Ac/Ib) in the management of acute pain after oral surgery.


METHODS
This was a single-center, single-dose, randomized, active-controlled, parallel-group study in healthy subjects who had undergone surgical extraction of > or =1 impacted third molar requiring bone removal. When patients reported at least moderate pain after dental surgery (score > or =5 on a 10-point scale), they were randomized to 1 of 2 treatment groups. The time to onset of analgesia was measured using a 2-stopwatch technique. The time to the onset of perceptible and meaningful pain relief, pain intensity, pain relief, patient's overall assessment, and adverse events were recorded for 6 hours after dosing.


RESULTS
One hundred twenty-eight subjects participated in the study, 64 in each treatment group. The 2 groups were similar in terms of baseline pain severity and demographic characteristics (mean age, 23.7 and 23.4 years in the Tr/Ac and Co/Ac/Ib groups, respectively; mean body weight, 58.5 and 60.3 kg). The median times to the onset of perceptible pain relief were a respective 21.0 and 24.4 minutes, and the median times to the onset of meaningful pain relief were 56.4 and 57.3 minutes. Mean total pain relief and the sum of pain intensity difference were also similar in the early period after dosing (0-4 hours). However, between 4 and 6 hours, Co/Ac/Ib was associated with significant differences in both variables compared with Tr/Ac (P < 0.05). Although similar through the 4-hour assessment, mean pain intensity difference was significantly greater with Co/Ac/Ib at 5 to 6 hours. The proportion of patients assessing their assigned treatment as good or better was significantly greater with Co/Ac/Ib compared with Tr/Ac (P < 0.05). The safety profile of Tr/Ac was comparable to that of Co/Ac/Ib.


CONCLUSIONS
In this small and selected group of subjects, the onset of analgesia and analgesic efficacy of Tr/Ac was comparable to that of Co/Ac/Ib. Tr/Ac provided rapid and effective analgesia for acute postoperative dental pain in this population.
Jung
Young-Soo
YS
Department of Oral and Maxillofacial Surgery, Oral Science Research Center, College of Dentistry, Yonsei University, Seoul, Korea.
Kim
Dong Kee
DK
Kim
Moon-Key
MK
Kim
Hyung-Jun
HJ
Cha
In-Ho
IH
Lee
Eui-Wung
EW
D000082:Acetaminophen / Q000008:administration & dosage / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000698:Analgesia; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D003061:Codeine / Q000008:administration & dosage / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010149:Postoperative Pain / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors; D014081:Tooth Extraction; D014147:Tramadol / Q000008:administration & dosage / Q000627:therapeutic use*
D000701:Analgesics, Opioid; D004338:Drug Combinations; D000082:Acetaminophen; D014147:Tramadol; D003061:Codeine; D007052:Ibuprofen