***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 1 Twelve healthy volunteers received a single oral dose of tenoxicam 20 mg on six occasions separated by 3 weeks . 2 The six occasions were : fasted overnight ; postpr and ial ; fasting and 15 ml aluminium hydroxide gel ; postpr and ial and 15 ml aluminium hydroxide gel ; fasting and 15 ml aluminium and magnesium hydroxide gel ; postpr and ial and 15 ml aluminium and magnesium hydroxide gel . 3 Twenty plasma sample s were collected over 15 days following dosing with tenoxicam . 4 The following kinetic parameters for plasma tenoxicam were compared : peak concentrations , time taken to reach peak concentrations , area under the plasma concentration-time curve ( AUC ) and half-life of elimination . 5 Food lengthened the time taken to reach peak tenoxicam concentrations ( 5.82 + /- 4.6 vs 1.84 + /- 1.0 h in the fasting state ; P less than 0.02 ) and marginally reduced the peak concentrations achieved . AUC was not affected by any of the different regimens . 6 These effects of food on tenoxicam bioavailability are unlikely to be of clinical significance during chronic dosing with the drug Compliance to nonsteroidal anti-inflammatory drug therapy can be compromised by gastrointestinal side effects . To overcome this problem , food , antacid , or sucralfate are often co-administered with nonsteroidal anti-inflammatory drugs . Three studies were conducted on three groups of 12 volunteers in order to determine the influence of food or sucralfate on the pharmacokinetics of naproxen and ketoprofen . In a crossover experimental design , the first group received a single dose ( 50 mg ) of ketoprofen with and without sucralfate ( 2 g ) . The second group received single ( 100 mg ) and multiple ( 100 mg twice daily for 5 days ) doses of enteric-coated ketoprofen with and without food . The third group received single ( 500 mg ) and multiple ( 500 mg twice daily ) doses of naproxen with and without sucralfate . Multiple blood sample s were drawn and analyzed by high-pressure liquid chromatography . Short- and long-term pharmacokinetic parameters were determined . Results in group 1 showed that neither  ketoprofen bioavailability nor maximal plasma concentration and time to reach maximal concentration were affected by the administration of sucralfate . However , in group 2 absorption of ketoprofen  was markedly affected by food . In the presence of food , maximal plasma concentration decreased from 10.7 to 6.3 micrograms/ml after single-dose administration and 12.1 to 8.0 micrograms/ml after multiple-dose administration . The time to reach maximal plasma concentration was also modified by food , increasing from 2.8 to 7.1 hours after single-dose and 2.8 to 7.6 hours after multiple-dose administration . Food caused a significant decrease in the bioavailability of ketoprofen ( over 40 percent ) following both single-dose ( 23.8 versus 13.1 micrograms.hour/ml ) and multiple-dose ( 29.3 versus 16.8 micrograms.hour/ml ) administration . Results obtained in group 3 showed that sucralfate reduced the absorption rate constant of naproxen , from 1.7 to 1.2 hours-1 and from 1.5 to 0.7 hour-1 following single- and multiple-dose administration , respectively . However , bioavailability of naproxen  was not affected by sucralfate administration . Overall , these studies have shown that sucralfate does not alter the pharmacokinetics of naproxen and ketoprofen ; the amount of drug absorbed remains constant . However , plasma concentrations of ketoprofen  after single- and multiple-dose administration were greatly affected by food , with a decrease of greater than 40 percent in bioavailability BACKGROUND Diclofenac potassium liquid-filled soft gelatin capsule ( DPSGC ) is an investigational formulation that uses dispersing agents design ed to facilitate rapid and consistent absorption of this NSAID . OBJECTIVE The aim of this study was to characterize the effects of food intake on the pharmacokinetic ( PK ) profile of oral DPSGC at doses of 25 and 50 mg . METHODS In this open-label , r and omized , single-dose ( 2 distinct doses ) , 2-way crossover bioavailability study , healthy adult volunteers were r and omly assigned to receive a single dose of DPSGC 25 or 50 mg after an overnight fast ( fasted condition ) or high-fat breakfast ( fed condition ) ( period 1 ) . After 7 days , the participants received the same dose under the opposite fed/fasted condition ( period 2 ) . Serial blood sample s were obtained before and through 6 hours after study drug administration . Concentrations of diclofenac in plasma were determined using HPLC , and PK profiles were studied using ANCOVA . Adverse events ( AEs ) were monitored and recorded on each in-clinic day . RESULTS Of 47 participants included in the study , 24 received the 25-mg dose of DPSGC and 23 received the 50-mg dose . The majority of participants were male ( 80.9 % ) , and the mean age was 28.6 years . The mean ( SD ) AUC values for the fasted and fed states were 691 ( 195 ) and 680 ( 184 ) ng x h/mL , respectively , with the 25-mg dose , and 1521 ( 377 ) and 1416 ( 366 ) ng . h/mL , respectively , with the 50-mg dose , suggesting that the extent of absorption was similar with both dietary conditions at each dose . Food intake was associated with decreases in C(max ) by nearly half in the 25-mg group ( fasted vs fed , 1156 [ 482 ] vs 686 [ 411 ] ng/mL , respectively ; P < 0.05 ) and the 50-mg group ( 2365 [ 1034 ] vs 1154 [ 592 ng/mL ; P < 0.05 ) and delayed T(max ) in the 25-mg group ( 0.49 [ 0.16 ] vs 1.02 [ 0.55 ] hours ; P < 0.05 ) and 50-mg group ( 0.51 [ 0.19 ] vs 1.28 [ 0.71 ] hours ; P < 0.05 ) . Two mild AEs ( nasal congestion and light-headedness ) were reported in 2 participants who received 25 mg under fed conditions and 50 mg under fasted conditions , respectively . CONCLUSIONS Food intake did not appear to affect the extent of absorption ( ie , total exposure ) of oral DPSGC at doses of 25 and 50 mg in these healthy adult volunteers . Both single doses appeared to be well tolerated Celecoxib pharmacokinetics was evaluated after single and multiple oral dosing ; after dosing in a solution and as a solid ; with and without food ; and after administration into different sites of the GI tract using dog . After oral dosing in a solution , celecoxib was rapidly absorbed and reached maximum concentrations by 1 h ; absorption was delayed another 1 to 2 h when administered as a solid . The absolute bioavailability of  celecoxib  was higher when given as a solution ( 64 - -88 % ) compared with capsule ( 22 - -40 % ) . The absorption of  celecoxib  given in a capsule was delayed by food , although systemic exposure increased by 3- to 5-fold . The systemic availability of celecoxib given intragastrically in solution was similar to that obtained following direct instillation into the duodenum , jejunum , or colon through a chronic intestinal access port . Collectively , these data suggest that celecoxib is a highly permeable drug that can be absorbed throughout the GI tract and that dissolution may be a rate-limiting factor for absorption from solid dosage forms . Unlike dogs , celecoxib given to humans with a high fat meal exhibits only a slight increase in AUC(0 - -infinity ) ( 11 % ) that is not clinical ly significant with regard to safety or efficacy . In humans , a lower dose and a longer GI residence time may promote the opportunity for absorption of a poorly soluble drug such as celecoxib that can be absorbed throughout the GI tract . This would minimize the effect of food on absorption ; as such , patients with arthritis can be given celecoxib with or without food Background Previous analysis of a single data set in acute pain following third molar extraction demonstrated a strong relationship between the speed of reduction of pain intensity and overall pain relief , as well as need for additional analgesia . Methods Individual patient data analysis of a single r and omized , double-blind trial of placebo , paracetamol 1000 mg , ibuprofen sodium 400 mg and ibuprofen-poloxamer 400 mg following third molar extraction .  Visual analogue scale pain intensity ( VASPI ) and other measurements were made at baseline , every 5–45 min , and at 60 , 90 , 120 , 180 , 240 , 300 and 360 min . Results Most patients produced consistent VASPI results over time . For placebo and paracetamol , few patients achieved low VASPI scores and maintained them . For both ibuprofen formulations , VASPI scores fell rapidly during the first hour and were then typically maintained until later re-medication . Analysis of all patients showed that rapid VASPI reduction in the first hour was strongly correlated with good overall pain relief ( high total pain relief over 0–6 h ) , and with lesser need for additional analgesia within 6 h. Results for this analysis were in very good agreement with a previous analysis , validating the relationship between fast initial pain intensity reduction and overall good pain relief in this setting . Conclusions In acute pain following third molar extraction , faster acting analgesic formulations provide earlier onset of pain relief , better overall pain relief and a less frequent need for additional analgesia , indicating longer lasting pain relief The effects of preceding food intake on the plasma concentrations of  R(-)-ibuprofen  and the pharmacologically active enantiomer S(+)-ibuprofen were investigated in healthy subjects . A single oral dose of 400 mg racemic ibuprofen was administered either fasting or following a st and ardized meal . As compared to fasting administration postpr and ial drug intake result ed in a clear reduction of R(- ) and S(+)- ibuprofen plasma concentrations mainly during the initial three hours . The ratio of S(+)/R(-)-ibuprofen postpr and ially was increased for Cmax and AUC o-tmax as well as for AUC o-in 
    Output:
    
RESULTS Bioavailability was not different between fasted and fed states .
Cmax was typically reduced , with greater reduction seen with more rapid absorption ( fed Cmax only 44 - 85 % of the fasted Cmax for aspirin , diclofenac , ibuprofen and paracetamol ) .
There is evidence that high , early plasma concentrations produces better early pain relief , better overall pain relief , longer lasting pain relief and lower rates of remedication .
Taking analgesics with food may make them less effective , result ing in greater population exposure .