***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: To determine the pharmacokinetic , subjective effects of a single 20 mg dose of nefopam administered either intravenously or orally in healthy volunteers , twenty-four healthy Caucasian men received 20 mg nefopam orally+placebo intravenous infusion and placebo orally+intravenous infusion of 20 mg nefopam with one week interval , in a double-blind , double-dummy cross-over study . Nefopam and desmethyl-nefopam  plasma concentrations were measured by HPLC with UV detection up to 48 hr after drug administration . Self-rating question naires ( Mood and vigilance Visual Analogue Scales , Addiction Research Centre Inventory ) and drug safety were investigated . The F value ( bioavailability ) of the parent drug was 0.36+/-0.13 . The AUCoral/AUCiv ratio of nefopam+desmethyl-nefopam was 0.62+/-0.23 . The half-life of nefopam was similar whether administered orally ( 5.1+/-1.3 hr ) or intravenously ( 5.1+/-0.6 hr ) . The half-life of desmethyl-nefopam was two to three times longer than that of the parent molecule ( orally : 10.6+/-3.0 versus 5.1+/-1.3 hr , P<10(-4 ) and intravenously : 15.0+/-2.4 versus 5.1+/-0.6 hr , P<10(-4 ) ) . As assessed by the Addiction Research Centre Inventory , no evidence of abuse liability in healthy , drug-naive volunteers was observed . On visual analogue scales , volunteers rated themselves as more drowsy , less alert , less energetic and less anxious after oral compared to intravenous administration . The AUC0 - ->24 hr of anxiety and energy parameters were not different after oral and intravenous administration : 90+/-142 versus 35+/-84 ( P=0.27 ) and 66+/-74 versus 46+/-54 mm x hr ( P=0.36 ) , respectively . The AUC0 - ->24 hr of drowsiness and alertness parameters were significantly greater after oral than after intravenous administration : 68+/-65 versus 27+/-30 ( P=0.005 ) and 54+/-63 versus 28+/-48 mm x hr ( P=0.03 ) , respectively . A clockwise hysteresis loop was observed for drowsiness in 16 out of 24 volunteers after oral administration . The results suggest that in healthy volunteers desmethyl-nefopam may contribute to the pharmacodynamic effects of single dose nefopam solution administered orally . This study shows a rather low bioavailability of nefopam given in intravenous solution when administered orally . Nevertheless , when the main metabolite desmethyl-nefopam is taken into account , the ratio of the areas under the curves is almost doubled In order to compare the morphine‐sparing effect , analgesic efficacy and tolerance of nefopam and propacetamol given at their highest recommended doses , 120 patients undergoing elective hepatic resection were r and omly assigned to receive postoperative intravenous patient‐controlled analgesia with morphine alone , or in combination with nefopam ( 20 mg.4 h‐1 ) or propacetamol ( 2 g.6 h‐1 ) . Compared with the control group ( 43 [ 7–92 ] mg ) , median [ range ] cumulative morphine consumption for 24 h after the study started was halved in the nefopam group ( 21 [ 3–78 ] mg , p < 0.001 ) and 20 % lower in the propacetamol group ( 35 [ 6–84 ] mg , p = 0.15 ) . Analgesia was superior in the nefopam group despite the lower morphine consumption . Adverse effects were comparable in the three groups , except for significantly more nausea in the control group ( 39 % vs. 17 and 26 % in the nefopam and propacetamol groups , respectively ) and more sweating in the nefopam group ( 17 % vs. 0 and 3 % in the control and propacetamol groups , respectively ) . Overall patient satisfaction was better ( p < 0.001 ) in patients given nefopam ( 97 % ) than those receiving morphine alone ( 82 % ) or propacetamol ( 74 % ) Nefopam ( NEF ) is a potent analgesic compound administered as a racemic mixture . Previous in vitro and in vivo studies with nefopam enantiomers have shown that (+)nefopam [ (+)NEF ] is substantially more potent than (-)nefopam [ (-)NEF ] . Differences between enantiomers have also been suggested in metabolic studies in vitro . The impact of these differences in vivo is not known because there is little or no information on the relative plasma concentrations of the enantiomers or on their kinetics . In this study , individual enantiomers of nefopam were synthesized and examined for acute toxicity in male and female rats and mice . Pharmacologic properties of enantiomers were examined using in vitro binding assays and antinociceptive tests in rats and mice . Additionally , a pharmacokinetic study was conducted in human volunteers . Subjects were administered 20 mg nefopam as Acupan(R ) either as a 5- or 20-min intravenous infusion . In a control phase , subjects were administered only vehicle .  Blood sample s were collected through the following 24 h. Plasma sample s were analyzed for individual enantiomers using a chiral assay developed for this purpose . The pharmacologic differences of previous studies were confirmed in receptor binding assays and in the hot plate and the formalin tests in mice . Neither enantiomer demonstrated substantial activity in the tail flick test in rats . No significant differences were revealed between LD(50 ) values of nefopam enantiomers after oral or intravenous administration in male and female rats or mice . There were no significant differences in AUC(0-infinity ) , C(max ) , or half-life between enantiomers following intravenous administration . Based on these findings , there is currently no compelling rationale to justify administering or monitoring individual enantiomers Ketorolac , ketoprofen and nefopam are often used in the treatment of  postoperative pain .  While nefopam is a non‐narcotic , non‐opioid central analgesic agent , ketorolac and ketoprofen are non‐steroidal anti‐inflammatory drugs , which , due to their prostagl and in‐synthetase inhibiting activity , have antiplatelet effects . In this study we investigated the effect of ketorolac , ketoprofen and nefopam on platelet function by performing bleeding time and in vitro platelet aggregation in 30 healthy volunteers ( 10 for each treatment ) before and 3h after drug administration . Nefopam did not affect bleeding time and platelet aggregation , while ketorolac and ketoprofen significantly prolonged bleeding time without significantly inhibiting platelet aggregation in response to adenosine diphosphate . The prolongation of bleeding time observed after ketorolac and ketoprofen may have clinical relevance and suggests that nefopam could be more safely administered for the treatment of postoperative pain , especially in patients with haemostatic defects or after high bleeding risk surgery Eighty‐two out patients who received general anaesthesia for surgical removal of maxillary or m and ibular third molars were given either diclofenac 75 mg or nefopam 20 mg intramuscularly for postoperative pain control . They and the control group were also allowed oral paracetamol as required . The results showed that there was no significant pain relief from these single intramuscular injections A double-blind , between-patient , two-dose comparison was comparison was performed with pethidine and nefopam in 100 subjects , the majority of whom were recovering from upper abdominal surgery . Either 15 or 30 mg of nefopam or 50 or 100 mg of pethidine were given by i.m . injection in a r and om order . All assessment s were made by the same observer on the first day after operation , at least 4 h after the previous analgesic injection . Nefopam 15 mg was equipotent with pethidine 50 mg , peak analgesia being achieved 1 h after the i.m . injection . Pethidine 100 mg provided significantly better pain relief than nefopam 30 mg , the latter being not more effective than nefopam 15 mg apart from the duration of analgesia which was longer . The incidence of nausea and vomiting was similar after both drugs . Sweating and tachycardia were observed more frequently after nefopam , whereas sedative side-effects were more common after pethidine A new analgesic , nefopam , is chemically distinct and pharmacologically unrelated to any presently known analgesic . A comparison was made of morphine and nefopam in 74 patients who required parenteral analgesia for moderate to severe postoperative and somatic pain , using a single administration , 2‐dose level , double‐blind design . A significant dose‐response curve was obtained with nefopam and with morphine , and there was no significant deviation from parallelism . The time‐effect curves for the 2 drugs were similar . The estimated relative potency of nefopam to morphine indicates that 20 mg of neJopam HCI is the approximate analgesic equal of 12 mg of morphine SO4 . There were no adverse effects with nefopam and one adverse reaction to morphine Arespiratory study has been done to compare the respiratory effects of a potent new analgesic ,  nefopam  , to morphine .  Morphine was a potent respiratory depressant at therapeutic dosage while nefopam was not The effect of a treatment versus controls may be expressed in relative or absolute terms . For rational decision-making , absolute measures are more meaningful . The number needed to treat , the reciprocal of the absolute risk reduction , is a powerful estimate of the effect of a treatment . It is particularly useful because it takes into account the underlying risk ( what would happen without the intervention ? ) . The number needed to treat tells us not only whether a treatment works but how well it works . Thus , it informs health care professionals about the effort needed to achieve a particular outcome . A number needed to treat should be accompanied by information about the experimental intervention , the control intervention against which the experimental intervention has been tested , the length of the observation period , the underlying risk of the study population , and an exact definition of the endpoint . A 95 % confidence interval around the point estimate should be calculated . An isolated number needed to treat is rarely appropriate to summarize the usefulness of an intervention ; multiple numbers needed to treat for benefit and harm are more helpful . Absolute risk reduction and number needed to treat should become st and ard summary estimates in r and omized controlled trials A r and omized , double‐blind , placebo‐controlled study was performed to assess the analgesic efficacy of intramuscular nefopam hydrochloride  after upper abdominal surgery . Patients received either 20 mg nefopam  ( n = 23 )  or matching placebo ( n = 26 ) , 90 min before surgery , immediately after surgery , and 6 , 12 and 18 h after the end of surgery . The 24‐h morphine requirements were measured using a patient‐controlled analgesia system delivering on‐dem and intravenous bolus doses of morphine . Pain was assessed using visual analogue scales . Patients receiving nefopam had a mean ( ± s.e.m . ) cumulative morphine consumption of 4.1 ± 0.8 mg in the first hour , compared with 8.5 ± 0.8 mg in the control group ( P < 0.01 ) . After 24 h the consumptions were 44.1 ± 7.2 mg and 62.5 ± 6.9 mg respectively ( P < 0.05 ) . The pain scores in both groups were similar . This study confirms that nefopam hydrochloride has significant analgesic effects and would be a useful supplement to morphine in the management of postoperative pain Opioids alone sometimes provide insufficient postoperative analgesia . Coadministration of drugs may reduce opioid use and improve opioid efficacy . We therefore tested the hypothesis that the administration of ketamine or nefopam to postoperative patients with pain only partly alleviated by morphine reduces the amount of subsequent opioid necessary to produce adequate analgesia . Patients ( n = 77 ) recovering from major surgery were given up to 9 mg of IV morphine . Those who still had pain were r and omly assigned to blinded administration of 1 ) isotonic saline ( control group ; n = 21 ) , 2 ) ketamine 10 mg ( ketamine group ; n = 22 ) , or 3 ) nefopam 20 mg ( nefopam group ; n = 22 ) . Three-milligram morphine boluses were subsequently given at 5-min intervals until adequate analgesia was obtained , until 60 min elapsed after the beginning of study drug administration , or until ventilation became insufficient ( respiratory rate < 10 breaths/min or saturation by pulse oximetry < 95 % ) . Supplemental morphine  ( i.e. , after test drug administration ) requirements were significantly more in the control group ( mean ± sd ; 17 ± 10 mg ) than in the nefopam ( 10 ± 5 mg ; P < 0.005 ) or ketamine ( 9 
    Output:
    
There is limited evidence from the published literature that nefopam may be a useful non-opioid analgesic in surgical patients .
The analgesic potency seems to be similar to non-steroidal anti-inflammatory drugs .