***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects , suggesting that combined administration may offer improved analgesia . Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen ( 200 mg ) and paracetamol ( 500 mg ) fixed-dose combination tablet . Methods Both studies were open-label , r and omised studies in healthy volunteers : Study 1 was a four-way crossover , single-dose study ; Study 2 was a two-way cross-over , repeat-dose study . Results Pharmacokinetic parameters for  ibuprofen and paracetamol  were similar for the combination and monotherapy tablets ( values falling within the 80 % to 125 % acceptable bioequivalence range ) except for the rate of absorption of paracetamol  from the combination ( tmax ) , which was significantly faster compared with monotherapy ( median difference 10 minutes ; p < 0.05 ) . Mean plasma concentrations of both drugs were higher , earlier , following administration of the combination tablet compared with monotherapy . Mean plasma levels at 10 and 20 minutes were 6.64 μg.mL-1 and 16.81 μg.mL-1 , respectively , for ibuprofen from the combination , compared with 0.58 μg.mL-1 and 9.00 μg.mL-1 , respectively , for monotherapy . For  paracetamol , mean plasma levels at 10 and 20 minutes were 5.43 μg.mL-1 and 14.54 μg.mL-1 , respectively , for the combination compared with 0.33 μg.mL-1 and 9.19 μg.mL-1 , respectively , for monotherapy . The rate of absorption of both ibuprofen and paracetamol  was significantly delayed when the combination tablet was administered in the fed versus fasted state ; median delay was 25 minutes for ibuprofen ( p > 0.05 ) and 55 minutes for paracetamol ( p < 0.001 ) . The pharmacokinetic parameters were comparable irrespective of whether the combination tablet was given twice or three times daily ; systemic exposure was , however , approximately 1.4 times greater for both drugs when given three times daily . Conclusions Administration of ibuprofen and paracetamol in a fixed-dose combination tablet does not significantly alter the pharmacokinetic profiles of either drug , except for enhancing the rate of paracetamol absorption , offering potential therapeutic benefits in relation to the onset of analgesia . Concentrations of both drugs reached previously reported therapeutic levels when the combination tablet was administrated in the fed or fasted state . Three times daily dosing may offer enhanced therapeutic effect for longer than twice daily dosing Objective : To compare the pharmacokinetic profiles of diclofenac potassium liquid-filled soft gelatin capsules ( DPSGC ) using patented ProSorb ® dispersion technology with an immediate-release , diclofenac potassium 50-mg comparator tablet in two open-label , single-dose , r and omized , crossover relative bioavailability studies in healthy volunteers . Methods : In Study 1 , volunteers ( n = 21 ) received DPSGC 50 mg or a diclofenac potassium 50-mg comparator tablet in two inpatient study periods . In Study 2 ( n = 54 ) , volunteers received DPSGC 25 mg , DPSGC  50 mg , or a diclofenac potassium 50-mg comparator immediate-release tablet in three inpatient study periods . Results : In both studies , DPSGC 50 mg displayed a significantly shorter Tmax and higher Cmax than the 50-mg diclofenac potassium comparator tablet . DPSGC 25 mg ( Study 2 ) produced a shorter Tmax ( 0.45 h ) and an equivalent Cmax ( 1125 ng/ml ) to the 50-mg comparator drug . Plasma diclofenac concentration – time courses for the diclofenac potassium 50-mg comparator tablet showed many low , delayed , or multiple peaks compared with DPSGC treatments . Conclusions : DPSGC 25 mg and 50 mg were more rapidly and consistently absorbed than diclofenac potassium 50-mg comparator tablets . The Cmax of DPSGC 25 mg was equivalent to the 50-mg diclofenac potassium comparator tablet . These characteristics may be beneficial when fast , consistent drug absorption is needed BACKGROUND Because of its enhanced pharmacokinetic characteristics , ibuprofen arginate might be expected to provide faster pain relief than st and ard ibuprofen formulations in patients experiencing acute pain . OBJECTIVE This study assessed the analgesic efficacy , speed of onset , and tolerability of ibuprofen arginate compared with a commercially available form of ibuprofen in patients with postoperative dental pain . METHODS Patients were r and omized to receive ibuprofen arginate 200 or 400 mg , ibuprofen 200 or 400 mg , or placebo in this multicenter , double-blind , double-dummy , parallel-group trial . Patients were observed for 6 hours after administration of a single dose of study medication . A repeated-dose , open-label phase followed . Pain intensity and pain relief were measured using traditional verbal descriptor scales ; onset of analgesia was assessed using 2 stopwatches to measure the time to achievement of specific pain relief criteria . RESULTS A total of 498 patients ( 219 men , 279 women ; mean age , 21.5 years ) participated in this study .  Baseline pain was moderate in 388 patients ( 78 % ) and severe in 110 patients ( 22 % ) . Meaningful pain relief was reached after a median of 29 and 28 minutes with ibuprofen arginate 200 and 400 mg , respectively , and after 52 and 44 minutes with ibuprofen 200 and 400 mg , respectively ( all , P < 0.05 ) . The percentages of patients who achieved meaningful pain relief within the first hour after treatment were 77.6 % and 83.7 % for ibuprofen arginate 200 and 400 mg , respectively , 61.0 % and 63.0 % for ibuprofen 200 and 400 mg , respectively , and 39.8 % for placebo . The differences between ibuprofen arginate and ibuprofen were statistically significant ( both doses , P < 0.05 ) . Significantly greater numbers of patients achieved meaningful pain relief with ibuprofen arginate 400 mg compared with placebo from 20 minutes through 6 hours and with ibuprofen arginate 200 mg from 30 minutes through 6 hours ( P < 0.05 ) . Compared with placebo , a greater number of patients achieved meaningful pain relief with ibuprofen 400 mg from 45 minutes through 6 hours ; with ibuprofen 200 mg . the corresponding interval was from I through 6 hours . After the first hour , pain reduction was similar for the similar doses of the 2 ibuprofen preparations . Median remedication times with both doses of ibuprofen arginate were similar to those with both doses of ibuprofen , ranging from 4.0 to 5.2 hours . Adverse-event profiles were similar between the 2 active medications . CONCLUSIONS Ibuprofen arginate was effective in this population of patients experiencing moderate to severe pain after surgical extraction of > or = 1 impacted third molar , with 16 to 24 minutes ' faster time to meaningful pain relief than with ibuprofen . The 2 formulations had similar tolerability profiles Objective : To assess the time of onset and difference in analgesic efficacy of oral dexketoprofen compared with oral diclofenac in patients with acute lower limb injury . Design : A prospect i ve , double blind , r and omised controlled trial . Interventions : Patients who fitted the study criteria were given either 25 mg oral dexketoprofen trometamol or 50 mg sodium diclofenac immediately after triage ; baseline and 15 minute pain scores were then recorded for one hour . Results : 122 patients were studied ( diclofenac = 57 and dexketoprofen = 65 ) . There were no significant differences in age , sex , type of injury , or baseline pain scores between the two groups . The differences in group mean pain scores between diclofenac and dexketoprofen at 15 , 30 , 45 , and 60 minutes were ; 0.53 ( 95 % confidence intervals −0.03 to 1.09 ) , 0.70 ( 0.16 to 1.24 ) , 0.89 ( 0.32 to 1.47 ) , and 0.83 ( 0.21 to 1.45 ) . Odds ratios for a decrease in pain score of at least 1 from baseline ( on the 11 point scale ) when given dexketoprofen rather than diclofenac at 15 , 30 , 45 , and 60 minutes were ; 2.66 ( 1.19 to 5.98 ) , 3.52 ( 1.60 to 7.73 ) , 4.48 ( 1.72 to 11.65 ) , and 5.54 ( 1.90 to 16.15 ) . Corresponding odds ratios for a decrease in pain score of ⩾2 were ; 6.88 ( 1.48 to 32.0 ) , 3.79 ( 1.59 to 9.01 ) , 5.19 ( 2.29 to 11.78 ) , and 5.87 ( 2.68 to 12.88 ) . Conclusions : Dexketoprofen trometamol is an effective and rapidly acting analgesic for the treatment of acute musculoskeletal injuries Onset and offset of dental pain relief by ibuprofen  following third molar extraction were modeled in a r and omized , double-blind , placebo-controlled , parallel-group , 8-hour study of patients receiving either a novel effervescent ibuprofen tablet ( 400 mg ; N = 30 ) , st and ard ibuprofen tablets ( Nurofen ( ® ) 2 × 200 mg ; N = 22 ) , or placebo ( N = 37 ) . An Emax model was fit to pain relief scores . Linear hazard models were used to analyze the time to first perceptible relief ( TFPR ) , the time to meaningful pain relief ( TMPR ) , and time to remedication ( REMD ) . Nomograms were created to correlate TFPR , TMPR , and REMD with different ibuprofen pharmacokinetic profiles . Effervescent ibuprofen was absorbed rapidly with 95 % completion within 15 minutes . Maximum pain relief score  by ibuprofen was 1.8 units greater than placebo , with an EC50 ( effect-site ) for ibuprofen concentration of 10.2 µg·mL(-1 ) . The likelihood to achieve TFPR and TMPR was doubled for every 10 µg·mL(-1 ) increase in ibuprofen plasma concentration . REMD risk decreased 40-fold as the categorical pain relief score increased from 0 to 3 . Rapid absorption of ibuprofen effervescent result ed in an earlier TFPR and TMPR , and a lower REMD rate than st and ard ibuprofen . The nomograms may be useful in predicting the onset and offset of new faster acting ibuprofen formulations , based on pharmacokinetic profiles 1 . A sensitive , stereospecific assay using gas chromatography-mass spectrometry ( GC/MS ) was established to measure the concentrations of the enantiomers of ibuprofen in small volumes ( 50 microliters ) of blister fluid . 2 . The concentrations of the enantiomers in blister fluid , assessed in eight patients , were similar to those in synovial fluid , both fluids behaving as peripheral compartments with respect to plasma . 3 . The mean rate constants of transfer of R-ibuprofen into ( 0.14 + /- 0.06 h-1 ) and out of ( 0.20 + /- 0.04 h-1 ) blister fluid were not significantly different from those for synovial fluid ( 0.19 + /- 0.12 h-1 , 0.34 + /- 0.11 h-1 , respectively ) . Similarly , the mean rate constants of transfer of S-ibuprofen into ( 0.22 + /- 0.07 h-1 ) and out of ( 0.27 + /- 0.08 h-1 ) blister fluid were not significantly different from those for synovial fluid ( 0.29 + /- 0.10 , 0.36 + /- 0.11 h-1 ) . However , the correlations were poor between the transfer constants for each of the enantiomers between plasma , and both blister and synovial fluid ( P > 0.2 ) . 4 . The complex rate constant of transfer of S-ibuprofen into blister fluid ( 0.22 + /- 0.07 h-1 ) was greater than that of R-ibuprofen ( 0.14 + /- 0.07 h-1 ) , which may be explained by the lesser protein binding of the S-enantiomer . ( ABSTRACT TRUNCATED AT 250 WORDS The speed of onset of analgesia following intra 
    Output:
    
Individual patient data analysis in dental pain demonstrated a strong correlation between more rapid reduction of pain intensity over 0 - 60 min and better pain relief over 0 - 6h .
Rapid initial reduction of pain intensity was also linked with reduced need for remedication .
Fast-acting formulations of ibuprofen demonstrated more rapid absorption , faster initial pain reduction , good overall analgesia in more patients at the same dose , and probably longer-lasting analgesia , but with no higher rate of patients reporting adverse events .
Formulation chemistry is of potential importance for analgesics