The effects and safety of dexibuprofen compared with ibuprofen in febrile children caused by upper respiratory tract infection (2024)

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

  • The analgesic and anti-inflammatory efficacy of dexibuprofen compared with ibuprofen in adults with osteoarthritis, rheumatoid arthritis and dental pain.

WHAT THIS STUDY ADDS

  • Dexibuprofen is as effective and tolerable as ibuprofen, and a dose of 5 mg kg−1 of dexibuprofen would be sufficient to control fever caused by upper respiratory tract infection in children.

AIM

To evaluate the antipyretic efficacy and tolerability of dexibuprofen compared with ibuprofen in children with fever caused by upper respiratory tract infection (URTI).

METHODS

The study population consisted of children aged 6 months to 14 years. At the time of visit to the hospital, the children had fever; the cause of fever was determined to be URTI by a paediatrician based on history taking and physical examination. The study was a multicentre, randomized, double-blind, controlled parallel group, comparative, Phase 3 clinical trial, conducted at three hospitals. By using a computer-based random assignment program, the subjects were allocated to the following three groups: 5 mg kg−1 dexibuprofen group, 7 mg kg−1 dexibuprofen group, and 10 mg kg−1 ibuprofen group.

RESULTS

In the clinical trial of the antipyretic action of dexibuprofen in patients with fever caused by URTI, there was no statistically significant difference in maximal decrease of temperature and mean time to become apyrexial among the 5 mg kg−1 dexibuprofen, 7 mg kg−1 dexibuprofen and 10 mg kg−1 ibuprofen groups (P > 0.05). There also was no significant difference in adverse drug reaction (P > 0.05).

CONCLUSIONS

Dexibuprofen is as effective and tolerable as ibuprofen. A dose of 5 mg kg−1 and 7 mg kg−1 dexibuprofen in place of 10 mg kg−1 ibuprofen would be sufficient to control fever caused by URTI in children.

Keywords: children, dexibuprofen, fever, ibuprofen, upper respiratory tract infection

Introduction

Ibuprofen is one of the most commonly prescribed antipyretic drugs for febrile children. Ibuprofen is a nonsteroidal anti-inflammatory drug, which apart from being an analgesic is known to have significant antipyretic and anti-inflammatory properties, and is being increasingly used to control fever. Worldwide clinical experience with ibuprofen confirms that it is well tolerated not only in adults but also in children, in whom advantageous antipyretic properties of this drug have been reported [15].

Ibuprofen is a racemic mixture of R(−) ibuprofen and S(+) ibuprofen in the ratio of 1 : 1. Dexibuprofen is a pharmacologically effective enantiomer of racemic ibuprofen. Racemic ibuprofen and dexibuprofen differ in their physicochemical properties, and R(−) ibuprofen can exhibit pharmacological action only after conversion into dexibuprofen [6]. However, such chiral inversion could generate two negative results. First, it confers a very complex pharmacokinetic and pharmacodynamic property to the molecule; thus, determination of the dose of racemic ibuprofen may become difficult between individuals [7], and factors including formulation type [8, 9], disease state [10] and other drugs [11] may influence the determination of dose of racemic ibuprofen. Second, it may cause toxicity such as formation of hybrid triglycerides by interfering with lipid metabolism [1217]. Based on these results, it can be assumed that an identical pharmacological efficacy could be exerted by smaller doses of dexibuprofen instead of racemic ibuprofen, and this may be a potential method to decrease side-effects.

The dose of ibuprofen for children >1 year old has already been established; it can be administered to children readily. On the other hand, studies on the efficacy and tolerability of dexibuprofen in children have not yet been conducted.

The administration of dexibuprofen may offer the advantage of delivering the well-known antipyretic, analgesic and anti-inflammatory properties of ibuprofen in a more efficient way, with a better safety profile than the racemic ibuprofen formulations. Based on this consideration, we designed this clinical trial to evaluate the antipyretic efficacy and tolerability of dexibuprofen oral drops compared with ibuprofen syrup.

Methods

Patients

The study population consisted of children aged 6 months to 14 years. All children were of Asian race. At the time of the visit to the hospital, the children had fever on the thermometer caused by upper respiratory tract infection (URTI). Children were defined to have fever when the temperature of the axillary fossa measured by a mercury glass thermometer was ≥38°C. URTI was diagnosed by a paediatrician based on a review of disease history and physical examination. The clinical definition of URTI was made when the patient had manifestations suggesting an upper respiratory infection, such as fever, sore throat, rhinorrhoea/nasal obstruction and cough, without signs of disease in the lower respiratory tract on physical examination, and had had <1 week of disease duration. The following criteria were used for the exclusion of children from the study. Children who had taken antipyretics within the last 4 h, children with a febrile crisis within the last 6 months, children with a disease history of gastrointestinal haemorrhage, children with a disease history pertinent to the kidney, lung, endocrine system and heart and for which they had undergone treatment within the last 6 months, children with neurological abnormalities, children with uncontrolled diabetes, children with a suspected lower respiratory tract infection and children determined to be psychologically unfit to participate in the clinical trial were excluded.

Prior to enrolment, parents or legal guardians were comprehensively informed about the clinical trial and gave written informed consent. The clinical studies were approved by the Korean Food and Drug Administration and by the Institutional Research Board of each institution. In addition, the trial was conducted in accordance with the ethical principles of the Declaration of Helsinki (South Africa Revision, October 1996).

Drugs

All drugs used for the study were provided by Hanmi Pharmaceuticals (Seoul, Republic of Korea). Dexibuprofen (12 mg ml−1) and ibuprofen (20 mg ml−1) were supplied in the form of syrup.

Study design

The study was a multicentre, randomized, double-blind, controlled parallel group, comparative, Phase 3 clinical trial. The main objective of this clinical study was to prove the hypothesis that the antipyretic efficacy of test drug dexibuprofen is not inferior to that of control drug ibuprofen. The sample size was calculated on the basis of the following assumptions. The mean change in temperature 4 h after a single dose between the dexibuprofen (treatment group) and ibuprofen (control group) was 1.42°C with a standard deviation of 0.85°C [18]. Also, we assumed that the clinical difference between the treatment and control groups was ≥30% reduction in temperature. The power of test was set 90% and significance level was 0.05. Considering an expected drop-out rate of 20%, the sample size was calculated to be 86 subjects in each group.

The study was conducted at three hospitals of the Catholic University of Korea (Uijeongbu St Mary's hospital and Our Lady of Mercy hospital) and Hanyang University Guri hospital. By using a computer-based random assignment program, subjects were randomly assigned to the following three groups: 5 mg kg−1 dexibuprofen group (n = 86), 7 mg kg−1 dexibuprofen group (n = 84), and 10 mg kg−1 ibuprofen group (n = 85).

All subjects were hospitalized and body temperature was re-evaluated. It was measured at different time points, i.e. 1, 2, 3, 4 and 6 h after the administration of experimental or control drugs based on their body weight.

Children were defined to have fever when the temperature of the axillary fossa measured by a mercury glass thermometer was ≥38°C. The tip of the mercury thermometer was placed slightly anterior to the centre of the armpit, maintained in this position for 10 min based on Khorshid et al. [19] and the temperature was measured. Older children were instructed to keep the thermometer appropriately placed in the armpit themselves, and for young children the parents were instructed to keep it in place.

After complete measurement of body temperature up to 6 h, the subjects were discharged depending on their condition. They were asked to visit the hospital 2 days later.

The antipyretic efficacy of each drug was determined by the reduction of temperature with time, the maximum decrease in temperature and the percentages of normalized temperature. Normal body temperature was defined as in the range 35.3–37.3°C and apyrexia as <38.0°C.

Physical examination, routine haematology and blood biochemistry analysis, and urinalysis were performed prior to drug administration and on day 3. Adverse events and concomitant therapy were assessed and recorded appropriately throughout the study period. At day 3, the overall efficacy and tolerability of the experimental drugs were assessed.

Statistical methods

At baseline, the characteristics of the three treatment groups were compared using analysis of variance (anova) for the quantitative parameters and the χ2 test for the qualitative parameters. The efficacy and tolerability parameters were also analysed using anova and χ2 test, respectively. All analysis was carried out using the software SPSS 10.0 for Windows (SPSS Inc., Chicago, IL, USA). P-values < 0.05 were interpreted as statistically significant.

Results

Patients’ characteristics

From November 2005 to June 2006, 258 children were enrolled in three hospitals – 82, 86 and 90 in each hospital. The children were randomly assigned to each study group with the same sample size of 86. However, three of these 258 children withdrew their consent to participate in the study before drug administration. Finally, 255 were administered the study drugs. Eighty-six children received 5 mg kg−1 dexibuprofen, 84 received 7 mg kg−1 dexibuprofen and 85 received 10 mg kg−1 ibuprofen. Three children (one from the 5 mg kg−1 dexibuprofen group and two from the 7 mg kg−1 dexibuprofen group) were excluded after taking the drugs because their body temperatures were not measured for 6 h after administration of the drugs. The efficacy and tolerability of the experimental drugs were evaluated in the above 255 children according to the intention-to-treat (ITT) analysis procedure.

A total of 23 subjects dropped out during the 3-day period. The reasons for the early termination were withdrawal of consent, taking additional antipyretics and having adverse effects. The data available from these patients prior to cessation of the study were considered for the ITT analysis.

The treatment groups were comparable with regard to their demographic characteristics, and no differences were noted (Table 1).

Table 1.

Demographic and clinical characteristics of the study groups at baseline

CharacteristicsDexibuprofen (5 mg kg−1) n = 86Dexibuprofen (7 mg kg−1) n = 84Ibuprofen (10 mg kg−1) n = 85P-value
Age (months)Mean ± SD47.3 ± 34.043.0 ± 33.145.0 ± 26.00.060*
Range6–1606–1626–161
Gender, n (%)Male44 (51.2)39 (46.4)53 (62.3)0.103
Female42 (48.8)45 (53.6)32 (37.7)
Height (cm)Mean ± SD100.3 ± 20.398.0 ± 20.493.3 ± 17.20.057*
Range70–15765–15864–152
Weight (kg)Mean ± SD17.4 ± 8.616.2 ± 7.616.5 ± 5.80.060*
Range8.4–53.07.5–53.06.0–52.0
Baseline temperature (°C)Mean ± SD38.7 ± 0.638.7 ± 0.738.6 ± 0.50.212*
Range38.0–40.138.0–41.138.0–40.2

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*

anova.

χ2 test.

Antipyretic effects

No differences were observed in temperature among the groups at 1, 2, 3, 4 and 6 h time points (P > 0.05, Figure 1). The results of other antipyretic analyses such as the changes in temperature with time, the maximum decrease in temperature, the percentages of children with reduction of temperature to normal range, and mean time to become apyretic were not significantly different among the groups (Table 2).

Figure 1.

The effects and safety of dexibuprofen compared with ibuprofen in febrile children caused by upper respiratory tract infection (1)

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Table 2.

Antipyretic activity

Antipyretic activityDexibuprofen (5 mg kg−1) n = 86Dexibuprofen (7 mg kg−1) n = 84Ibuprofen (10 mg kg−1) n = 85P-value
Reduction of temperature at 6 hMean ± SD0.8 ± 1.00.9 ± 1.10.9 ± 0.90.598*
Maximum decrease in temperature (°C)Mean ± SD2.0 ± 0.62.0 ± 0.81.9 ± 0.60.471*
Range0.8–3.30.5–4.70.4–3.4
Number (percentage) of normalized temperaturen (%)29 (33.7)35 (42.7)40 (47.0)0.203
Mean time to become apyrexic (h)Mean ± SD2.0 ± 0.82.0 ± 0.72.0 ± 0.80.905*
Range1–41–41–4

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*

anova.

χ2 test. Normal range of temperature: 35.3–37.3°C. Apyrexic: <38.0°C.

Safety

In 255 children, 49 adverse drug reactions of mild to moderate level were reported in 32 children (12.7%) during the study; of these, 11 in the 5 mg kg−1 dexibuprofen, 11 in the 7 mg kg−1 dexibuprofen and 10 in the 10 mg kg−1 ibuprofen group, respectively.

Although there were slightly more adverse drug reactions, primarily gastrointestinal symptoms in the 7 mg kg−1 dexibuprofen group, there were no significant differences in the occurrence of adverse reactions among the three groups (P > 0.05). The adverse reactions included diarrhoea, constipation, nausea, vomiting, abdominal pain, decreased oral intake, irritability, facial oedema, skin rash, elevated liver enzyme level and thrombocytopenia (Table 3).

Table 3.

Number of children with adverse reactions

NatureDexibuprofen (5 mg kg1) n = 86Dexibuprofen (7 mg kg1) n = 84Ibuprofen (10 mg kg1) n = 85P-value
Nausea010
Vomiting3640.545*
Diarrhoea4530.758*
Constipation010
Abdominal pain010
Poor oral intake100
Irritability010
Skin rash304
Facial oedema100
Elevated liver enzyme level5320.497*
Thrombocytopenia001
Total1718140.707*

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*

χ2 test.

Discussion

The clinical study was aimed at determining whether dexibuprofen has an antipyretic activity and tolerability compared with ibuprofen in febrile children caused by URTI. The present trial has shown that the antipyretic efficacy and frequency of side-effects of 5 mg kg−1 and 7 mg kg−1 dexibuprofen were similar to those of 10 mg kg−1 ibuprofen.

Ibuprofen exists in equal amounts of racemic mixture of S(+) and R(–) enantiomers [20, 21]. Dexibuprofen is the S(+) (dextrorotatory)-enantiomer of ibuprofen and accounts for virtual pharmacodynamic activities of the racemic compound [2124]. They inhibit the synthesis of prostaglandin and thromboxanes via blockade of cyclooxygenase enzymes. As an inhibitor of prostaglandin biosynthesis in vitro, dexibuprofen is >100 times as potent as the R(–)-enantiomer [23, 25]; it has been suggested that any observable in vitro effect of R(−) ibuprofen is due to the small amount of dexibuprofen present as an impurity [23].

In vivo, the R(−)-enantiomer of racemic ibuprofen undergoes unidirectional enzymatic chiral inversion to S(+)-enantiomer. This occurs to the extent of approximately 65%; on the other hand, there is no bioinversion of S(+) to R(−) ibuprofen [20, 21, 26, 27]. Although most of its inactive enantiomer is converted into the active form, the proponents of dexibuprofen suggest disadvantages of the racemic drug. It is argued that the conversion of racemic ibuprofen to S(+) ibuprofen results in variability in clinical responses, including delayed onset of activity and difficulty in achieving an optimal dose. For example, the extent of chiral inversion varies among osteoarthritis patients being treated with racemic ibuprofen, the fractional inversion of R(–) ibuprofen varying between 35 and 85% [7]. Formulation type [8, 9], disease state [10] and other drugs such as clofibrate [11] have been demonstrated to influence the chiral inversion of R(–) ibuprofen after dosing with the racemate. It is also felt that the formation of coenzyme A thioester during bioinversion of R(−) ibuprofen to S(+) ibuprofen may result in toxic effects such as interference in lipid anabolism/catabolism. For example, in rats the formation of hybrid triglycerides containing ibuprofen in place of endogenous fatty acids has been demonstrated after dosing with R(−) ibuprofen, but not S(+) ibuprofen [28]. These ‘hybrid triglycerides’ were deposited in adipose tissue, forming long-lasting reservoirs from which the drug was slowly released. At present the clinical consequences of the participation of the R-enantiomers of ibuprofen and other profens in lipid metabolism are unknown. R(−) ibuprofen bioactivation is susceptible to biological factors and certain drugs [23, 26, 29]. There are some clinical data to support these contentions [20, 23]; In a single-dose, double-blind, parallel-group study subjects received either 200 mg S(+) ibuprofen, 400 mg S(+) ibuprofen, 400 mg racemic ibuprofen, or placebo. Both doses of S(+) ibuprofen resulted in significantly greater analgesia over the first 60 min in comparison with racemic ibuprofen or placebo [29].

We have been unable to find any studies which compared the antipyretic effects of dexibuprofen and racemic ibuprofen. Some studies have compared dexibuprofen and racemic ibuprofen in diseases other than fever. In randomized uncontrolled studies that compared with ibuprofen or diclofenac, usual daily doses of dexibuprofen, 900 to 1200 mg, was efficacious for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and other rheumatic diseases [3032]. The efficacy of dexibuprofen and ibuprofen was comparable when dexibuprofen was administered at a 50% lower dose [20, 31, 32]. However, the period of these studies was short and not placebo controlled, meaning most of them suffered from deficiencies in design and implementation, and dexibuprofen has not been compared with placebo. Our study was unique in comparing antipyretic efficacy in children. However, it has the limitation of lacking a placebo control. For a more adequate assessment of efficacy, a well-controlled study of sufficient duration is required.

When given for the treatment of acute pain following the third molar extraction, the pain relief provided by single doses of 200 and 400 mg dexibuprofen was statistically superior to that of 400 mg racemic ibuprofen and placebo during the first hour post ingestion; 400 mg dexibuprofen (but not 200 mg dexibuprofen) remained statistically superior to 400 mg ibuprofen at 2 and 3 h post ingestion, whereas all regimens exerted similar analgesic effects during 4 to 6 h post ingestion. The incidence of adverse effects did not differ between the groups [29].

In other studies, dexibuprofen and ibuprofen at a dose ratio of 1 : 2 have shown comparable analgesic and anti-inflammatory activity [31, 32]. Twenty-four patients with chronically inflammatory and degenerative rheumatic disease were treated for two periods of 8 days. The initial dose was 300 mg S(+) ibuprofen or 600 mg racemate three times per day, and doses were adjusted to the complaints of the individual patient. The main end-point was the amount of drug required to achieve a condition satisfactory to the patient. They suggested that, with reference to the initial dose of racemate, 52% of S(+) ibuprofen and 99% racemate were sufficient to obtain the same results [32].

Racemic ibuprofen consists of equal portions of S(+) ibuprofen and R(−) ibuprofen. On a pharmacokinetic basis, the bioinversion of R(−) to S(+) ibuprofen following the administration of the racemic compound suggests that the dose of dexibuprofen should be higher than that of the S(+) ibuprofen portion of the racemate in order to provide patients with an equivalent amount of therapeutically active drug. Some investigators have recommended that multiplying the dose of racemic ibuprofen by 0.66 to obtain the dose of dexibuprofen alone may result in equivalent oral absorption [20]. However, limited clinical data support this concept [20]. Further clinical studies that evaluate this type of regimen [e.g. daily doses of 1800 mg racemic ibuprofen vs. 1200 mg (approximate) dexibuprofen] are warranted. Based on the above data, we obtained the dose of dexibuprofen by multiplying the dose of racemic ibuprofen (10 mg kg−1) by 0.5 (5 mg kg−1) and 0.66 (7 mg kg−1).

Potential advantages of dexibuprofen over racemic ibuprofen include lesser toxicity, greater clinical efficacy and lesser variability in therapeutic effects; furthermore, the dose optimization of dexibuprofen is easy, i.e. at half the dose of ibuprofen. This clinical study does not show that dexibuprofen has a major therapeutic advantage over ibuprofen. However, considering the above descriptions in this study, the possibility of dexibuprofen having clinical advantages over racemic ibuprofen deserves further investigation to determine how dexibuprofen may be different from racemic ibuprofen in relation to patient condition, formulation type, and interaction with other drugs. We determined the body temperatures at the 1, 2, 3, 4 and 6-h time points because the peak reduction in fever occurs 2–4 h after oral dosing of ibuprofen [33]. This study has also shown the lowest body temperature at 2–4 h in three of the experimental groups (Figure 1).

In conclusion, in our clinical trial on its antipyretic action, dexibuprofen offered no demonstrable major advantage over ibuprofen, despite the theoretical pharmacokinetic and pharmacodynamic considerations. However, the efficacy and tolerability of 5 mg kg−1 and 7 mg kg−1 dexibuprofen were not different from those of 10 mg kg−1 ibuprofen statistically. Thus, dexibuprofen can be considered to be as effective and tolerable as ibuprofen for children with fever caused by URTI. Dexibuprofen 5 mg kg−1 or 7 mg kg−1 would be sufficient in place of 10 mg kg−1 ibuprofen.

Competing interests

None declared.

Acknowledgments

We thank Jin Gyeony Kim, the director of pharmacist's office at Uijeongbu St Mary's Hospital for assistance in getting the approval of the Institutional Research Board. We also thank Professor Hyeon Woo Kim and CMC Clinical Research Coordinating Center for statistical advice. The sponsor of this clinical trial was Hanmi Pharmaceuticals, Co., Korea.

REFERENCES

  • 1.Amdekar YK, Desai RZ. Antipyretic activity of ibuprofen and paracetamol in children with pyrexia. Br J Clin Pract. 1985;39:140–3. [PubMed] [Google Scholar]
  • 2.Wilson TJ. Clinical pharmacology of paediatric antipyretic drugs. Ther Drug Monit. 1984;7:2–11. doi: 10.1097/00007691-198503000-00002. [DOI] [PubMed] [Google Scholar]
  • 3.Simon RE. Ibuprofen suspension: pediatric antipyretic. Pediatr Nurs. 1996;22:118–20. [PubMed] [Google Scholar]
  • 4.Marriott SC, Stephenson TJ, Hull D, Pownall R, Smith CM, Butler A. A dose ranging study of ibuprofen suspension as an antipyretic. Arch Dis Child. 1991;66:1037–41. doi: 10.1136/adc.66.9.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Autret E, Breart G, Jonville AP, Courcier S, Lassale C, Gohers JM. Comparative efficacy and tolerance of ibuprofen syrup and acetaminophen syrup in children with pyrexia associated with infectious diseases and treated with antibiotics. Eur J Clin Pharmacol. 1994;46:197–201. doi: 10.1007/BF00192548. [DOI] [PubMed] [Google Scholar]
  • 6.Leising G, Resel R, Stelzer F, Tasch S, Lanziner A, Hantich G. Physical aspects of dexibuprofen and racemic ibuprofen. J Clin Pharmacol. 1996;36:3S–6S. [PubMed] [Google Scholar]
  • 7.Rudy AC, Bradley JD, Ryan SI, Kalasinski LA, Xiaotao Q, Hall SD. Variability in the disposition of ibuprofen enantiomers in osteoarthritis patients. Ther Drug Monit. 1992;14:464–70. doi: 10.1097/00007691-199212000-00005. [DOI] [PubMed] [Google Scholar]
  • 8.Aiba T, Tse MM, Lin ET, Koizumi T. Effect of dosage form on stereoisomeric inversion of ibuprofen in volunteers. Biol Pharm Bull. 1999;22:616–22. doi: 10.1248/bpb.22.616. [DOI] [PubMed] [Google Scholar]
  • 9.Mehva R, Jamali F. Pharmacokinetic analysis of the enantiomeric inversion of chiral nonsteroidal antiinflammatory drug. Pharm Res. 1988;5:76–9. doi: 10.1023/a:1015979915771. [DOI] [PubMed] [Google Scholar]
  • 10.Jamali F, Kunz-Dober CM. Pain-mediated altered absorption and metabolism of ibuprofen: an explanation for decreased serum enantiomer concentration after dental surgery. Br J Clin Pharmacol. 1999;47:391–6. doi: 10.1046/j.1365-2125.1999.00902.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Scheuerer S, Hall SD, Williams KM, Geisslinger G. Effect of clofibrate on the chiral inversion of ibuprofen in healthy volunteers. Clin Pharmacol Ther. 1998;64:168–76. doi: 10.1016/S0009-9236(98)90150-3. [DOI] [PubMed] [Google Scholar]
  • 12.Evans AM. Pharmacodynamics and pharmacokinetics of the profens: enantioselectivity, clinical implications, and special reference to S(+)-ibuprofen. J Clin Pharmacol. 1996;36:7S–15S. [PubMed] [Google Scholar]
  • 13.Evans AM. Enantioselective pharmacodynamics and pharmacokinetics of chiral non-steroidal anti-inflammatory drug. Eur J Clin Pharmacol. 1992;42:237–56. doi: 10.1007/BF00266343. [DOI] [PubMed] [Google Scholar]
  • 14.McCormack K, Brune K. Dissociation between the antinociceptive and anti-inflammatory effects of the nonsteroidal anti-inflammatory drugs. Drugs. 1991;41:533–47. doi: 10.2165/00003495-199141040-00003. [DOI] [PubMed] [Google Scholar]
  • 15.Hutt AJ, Caldwell J. The metabolic chiral inversion of 2-arylpropionic acids – a novel route with pharmacological consequences. J Pharm Pharmacol. 1983;35:693–704. doi: 10.1111/j.2042-7158.1983.tb02874.x. [DOI] [PubMed] [Google Scholar]
  • 16.Wechter WW. Drug chirality: on the mechanism of R-aryl propionic acid class NSAIDs. Epimerization in humans and the clinical implications for the use of racemates. J Clin Pharmacol. 1992;34:1036–42. doi: 10.1002/j.1552-4604.1994.tb01977.x. [DOI] [PubMed] [Google Scholar]
  • 17.Evans AM. Comparative pharmacology of S(+)-ibuprofen and (RS)-ibuprofen. Clin Rheumatol. 2001;1(Suppl.):S9–14. doi: 10.1007/BF03342662. [DOI] [PubMed] [Google Scholar]
  • 18.Autret E, Reboul-Marty J, Henry-Launois B, Laborde C, Courcier S, Goehrs JM, Languillat G, Launois R. Evaluation of ibuprofen versus aspirin and paracetamol on efficacy and comfort in children with fever. Eur J Clin Pharmacol. 1997;51:367–71. doi: 10.1007/s002280050215. [DOI] [PubMed] [Google Scholar]
  • 19.Khorshid L, Eser I, Zaybak A, Yapucu U. Comparing mercury-in-glass, tympanic and disposable thermometers in measuring body temperature in healthy young people. J Clin Nurs. 2005;14:496–500. doi: 10.1111/j.1365-2702.2004.01076.x. [DOI] [PubMed] [Google Scholar]
  • 20.Gabard B, Nirnberger G, Schiel H, Mascher H, Kikuta C, Mayer JM. Comparison of the bioavailability of dexibuprofen administered alone or as part of racemic ibuprofen. Eur J Clin Pharmacol. 1995;48:505–11. doi: 10.1007/BF00194342. [DOI] [PubMed] [Google Scholar]
  • 21.Cheng H, Rogers JD, Demetriades JL, Holland SD, Seibold JR, Depuy E. Pharmacokinetics and bioinversion of ibuprofen enantiomers in humans. Pharm Res. 1994;11:824–30. doi: 10.1023/a:1018969506143. [DOI] [PubMed] [Google Scholar]
  • 22.Eller N, Kollenz CJ, Schiel H, Kikuta C, Mascher H. Pharmacokinetics of dexibuprofen administered as 200 mg and 400 mg film-coated tablets in healthy volunteers. Int J Clin Pharmacol Ther. 1998;36:414–7. [PubMed] [Google Scholar]
  • 23.Mayer JM, Testa B. Pharmacodynamics, pharmacokinetics and toxicity of ibuprofen enantiomers. Drugs Future. 1997;22:1347–66. [Google Scholar]
  • 24.Siemon D, de Vries JX, Stotzer F, Walter-Sack I, Dietl R. Fasting and postprandial disposition of R(−)- and S(+)-ibuprofen following oral administration of racemic drug in healthy individuals. Eur J Med Res. 1997;2:215–9. [PubMed] [Google Scholar]
  • 25.Levine MAH, Walker SE, Paton TW. The effect of food or sucralfate on the bioavailability of S(+) and R(−) enantiomers of ibuprofen. J Clin Pharmacol. 1992;32:1110–4. [PubMed] [Google Scholar]
  • 26.Rudy AC, Knight PM, Brater DC, Hall SD. Stereoselective metabolism of ibuprofen in humans: administration of R-, S- and racemic ibuprofen. J Pharmacol Exp Ther. 1991;259:1133–9. [PubMed] [Google Scholar]
  • 27.Kelley MT, Walson PD, Edge JH, Cox S, Mortensen ME. Pharmacokinetics and pharmacodynamics of ibuprofen isomers and acetaminophen in febrile children. Clin Pharmacol Ther. 1992;52:181–9. doi: 10.1038/clpt.1992.128. [DOI] [PubMed] [Google Scholar]
  • 28.Williams K, Day R, Knihinicki R, Duffield A. The stereoselective uptake of ibuprofen enantiomers into adipose tissue. Biochem Pharmacol. 1986;35:3403–5. doi: 10.1016/0006-2952(86)90443-0. [DOI] [PubMed] [Google Scholar]
  • 29.Dionne RA, McCullagh L. Enhanced analgesia and suppression of plasma beta-endorphin by the S(+)-isomer of ibuprofen. Clin Pharmacol Ther. 1998;63:694–701. doi: 10.1016/S0009-9236(98)90094-7. [DOI] [PubMed] [Google Scholar]
  • 30.Chlud K. Evaluation of tolerance and efficacy of S(+)-ibuprofen (Seractil) in daily practice: a postmarketing-surveillance study in 1400 patients (abstract CS1) J Clin Pharmacol. 1995;35:938. [Google Scholar]
  • 31.Rahlfs VW, Stat C. Reevaluation of some double-blind, randomized studies of dexibuprofen (Seractil): a state-of-the-art overview. Studies in patients with lumbar vertebral column syndrome, rheumatoid arthritis, distortion of the ankle joint, gonarthrosis, ankylosing spondylitis, and activated coxarthrosis. J Clin Pharmacol. 1996;36:33S–40S. [PubMed] [Google Scholar]
  • 32.Klein G, Neff H, Kullich W, Phleps W, Kollenz CJ. S(+) versus racemic ibuprofen. Lancet. 1992;339:681. doi: 10.1016/0140-6736(92)90842-q. [DOI] [PubMed] [Google Scholar]
  • 33.Schrefer J. Mosby's GenRx. 11th edn. St. Louis, MO: Mosby, Inc; 2001. pp. III-1269–73. [Google Scholar]
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