Fever is a common clinical sign in pediatric practice and a major reason for outpatient consultations and hospital admissions globally. It is a physiological reaction to infection or inflammation, brought about by an increase in the hypothalamic temperature set point. Although fever is a protective response that supports the host's immune system, sustained high fever may induce discomfort, irritability, diminished oral intake, and dehydration in the host, as well as high levels of stress and anxiety for caregivers. Thus, the goal of antipyretic therapy is to make the patient more comfortable and to alleviate symptoms associated with fever, not to normalize body temperature [1,2]. Acute febrile diseases account for a significant percentage of morbidity among children, especially in developing countries, where infectious diseases are still common. The incidence of childhood fever remains high due to viral respiratory tract diseases, bacterial diseases, gastrointestinal diseases, urinary tract diseases, and tropical diseases. In Pakistan, which is a resource-poor country, the burden of febrile illnesses is further compounded by delayed access to health care, sub-optimal levels of immunization coverage, and lack of diagnostic facilities. Thus, immediate and appropriate fever control is important for enhancing patients' comfort, supporting recovery, and preventing unnecessary hospital admissions [3]. The mainstay of pharmacologic treatment of fever in pediatric patients is the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Of these, ibuprofen has been widely accepted due to its efficacy, long duration of action, and favorable safety profile compared with other antipyretics. There are two optical isomers of ibuprofen, R(-)-ibuprofen and S(+)-ibuprofen, which are a racemic mixture. S(+) only, however, has significant pharmacological activity in that it inhibits the activity of cyclooxygenase enzymes that are involved in prostaglandin synthesis, which decreases fever, inflammation, and pain [4,5]. Dexibuprofen is the S(+)-isomer of ibuprofen, which is the active ingredient. Dexibuprofen has similar therapeutic effects at about half the dose of traditional ibuprofen because it contains only the active isomer. In previous pharmacological studies, the bioavailability of dexibuprofen is superior to that of ibuprofen: it is more water-soluble, its gastrointestinal absorption is rapid, and it has the same safety profile as ibuprofen while eliminating unnecessary exposure to the inactive R(-)-enantiomer. The pharmacokinetic benefits suggest that dexibuprofen may be more effective at reducing fever and have a lower incidence of side effects [6]. There have been several clinical trials comparing the efficacy of dexibuprofen with ibuprofen in children with fever, but the results have been inconsistent. Several studies have shown a more hypothermic effect after dexibuprofen, and others have shown similar therapeutic effectiveness. These conflicting observations may be due to differences in study populations, treatment regimens, dosage, and the methods used to assess outcomes. Additionally, there is limited evidence comparing the effectiveness of these drugs in Pakistani children [7,8]. The important clinical implications of finding the most effective antipyretic agent are made more significant by the high prevalence of febrile illnesses and the common use of NSAIDs in pediatric practice. Higher effectiveness in lowering temperature at a lower dose can lead to better treatment outcomes, with less drug exposure and fewer side effects. Thus, a randomized controlled trial was conducted in the Pediatric Department of Hayatabad Medical Complex, Peshawar, to compare the efficacy of dexibuprofen with that of ibuprofen in febrile children. The results of this research could inform evidence-based clinical decision-making and help select the best antipyretic therapy in everyday pediatric practice [9].

Study Objective

To assess the effectiveness of dexibuprofen compared with ibuprofen in lowering body temperature in febrile children by measuring the mean difference in axillary temperature 4 hours after drug administration.

Study Design and Setting

This cross-sectional study was conducted in the Department of Pediatrics at Hayatabad Medical College, Peshawar, Pakistan, from 30 April 2019 to 30 October 2019.

Participants

Fifty-eight children were excluded, leaving 150 febrile children aged between 6 months and 12 years with an axillary temperature ≥38°C enrolled. Eligible participants of either sex were randomly allocated into two equal groups (75 participants each). Children who lacked sufficient clinical information or had contraindications to either study medication were excluded. Parents/legal guardians provided written informed consent before enrollment.

Sample Size Calculation

Sample size was determined using the WHO sample size calculator for a difference in mean temperature reduction between dexibuprofen and ibuprofen, as reported earlier. To obtain sufficient statistical power, a total of 150 children were needed, with 75 per treatment group (1:1 randomization).

Inclusion Criteria

• Children between the ages of 6 months and 12 years.
• Axillary body temperature ≥38°C.
• Either male or female.
• Patients admitted with an acute febrile illness and antipyretic therapy.
• Written informed consent obtained from parents/legal guardians.

Exclusion Criteria

• Hypersensitivity to dexibuprofen or ibuprofen.
• Hepatic, renal, or gastrointestinal disease, especially severe.
• History of NSAID-induced bronchial asthma.
• If someone has taken another painkiller within the last 6 hours.
• Children who are very sick and will need intensive care or emergency treatment.

Diagnostic and Management Strategy.

Armpit temperature was taken with a calibrated mercury thermometer. Children eligible for study were randomized to receive dexibuprofen 5 mg/kg or ibuprofen 10 mg/kg. Four hours of hourly temperature monitoring were conducted, and standard pediatric care was administered for support.

Statistical Analysis

The data have been analyzed with SPSS version 22.0. Mean value and standard deviation were used to present continuous variables, while frequencies and percentages were used for categorical variables. Independent-samples Student's t-test was used to compare mean temperature reduction among groups, and the Chi-square test was used to compare categorical variables. A p-value < 0.05 was considered statistically significant.

A total of 150 febrile children were enrolled and randomly allocated into two equal groups, with 75 participants receiving dexibuprofen and 75 participants receiving ibuprofen. The mean age was 7.0 ± 4.29 years in the dexibuprofen group and 7.0 ± 3.98 years in the ibuprofen group. Male participants constituted 65% (n=49) of the dexibuprofen group and 68% (n=51) of the ibuprofen group, while females accounted for 35% (n=26) and 32% (n=24), respectively. Baseline demographic characteristics were comparable between both treatment groups (p>0.05). Following administration of the study medications, both groups demonstrated a reduction in body temperature; however, the reduction was greater in children receiving dexibuprofen. The mean decrease in body temperature after four hours was 1.94 ± 0.81°C in the dexibuprofen group compared with 0.97 ± 0.88°C in the ibuprofen group. This difference indicated superior antipyretic efficacy of dexibuprofen. No serious adverse drug reactions were observed during the study period, and both medications were well tolerated. Overall, dexibuprofen achieved a greater reduction in temperature than conventional ibuprofen, suggesting improved clinical effectiveness in managing fever among pediatric patients.

Table 1. Baseline Demographic Characteristics of the Study Participants (N = 150)

Values are presented as mean ± standard deviation or frequency (%). No statistically significant differences were observed in baseline demographic characteristics between the two treatment groups.

Table 2. Comparison of Mean Body Temperature Reduction After Four Hours

Data are expressed as mean ± standard deviation. An independent-samples Student's t-test was used to compare the mean temperature reduction between groups. Statistically significant at p < 0.05.

Table 3. Gender Distribution of Study Participants

Distribution of male and female participants in both treatment groups. Gender distribution was comparable between groups, with no statistically significant differences.

Table 4. Summary of Treatment Outcomes

Dexibuprofen demonstrated a significantly greater reduction in body temperature than ibuprofen. No serious adverse events were reported during the four-hour observation period.

In the present study, 150 febrile children, aged 6 months to 12 years, were randomly assigned to receive either dexibuprofen or ibuprofen. A total of 150 children aged 6 months to 12 years with fever were randomly allocated to receive either dexibuprofen or ibuprofen. The results showed that after 4 hours of treatment, dexibuprofen had a larger mean decrease in body temperature than ordinary ibuprofen. Demographic data (age and sex distribution) at baseline were similar between the two groups, indicating that the observed change in temperature was more likely attributable to the intervention itself than to other factors. These results suggest that dexibuprofen is an effective antipyretic drug for treating pediatric fever [10,11]. This observed decrease in temperature with dexibuprofen is biologically plausible, as it is the pharmacologically active S(+)-enantiomer of racemic ibuprofen. Dexibuprofen is the therapeutically active isomer of ibuprofen; it is not found in conventional ibuprofen and is absorbed more rapidly and is more bioavailable than ibuprofen. This pharmacologic benefit might account for the greater reduction in body temperature observed in the current study at a lower dose [12]. Similar results were obtained in a randomized clinical trial by Adnan et al. (2021), who included 150 febrile children and found that dexibuprofen resulted in significantly lower body temperatures 4 hours after administration compared with ibuprofen (p<0.001). The authors found that both medications were effective, but dexibuprofen was more effective as an antipyretic agent, consistent with the results of this study [13]. A recent multicenter, randomized controlled trial in 2025, however, involving 281 children, found that dexibuprofen was not inferior to ibuprofen. The investigators noted similar decreases in axillary temperature and fever clearance rates, with no difference in adverse events between treatment groups. These results indicate that dexibuprofen is effective in controlling fever across all trials. Still, its effectiveness relative to ibuprofen may depend on patient characteristics, the origin of the fever, dosage regimens, and study design [14]. Several reasons may account for the difference between our trial results and those of the recent Chinese trial. Children in the current study had a wide variety of febrile illnesses in a tertiary care hospital. In contrast, the 2025 trial focused mainly on upper respiratory tract infections and included a larger, multicenter population. However, variability in environmental conditions, nutritional status, genetic differences, baseline disease severity, and health care settings could also contribute to variation in responses to antipyretics. Additionally, the timing of temperature sampling and the definition of outcomes varied across studies, which could have contributed to variation in reported effectiveness [15]. The effectiveness of ibuprofen-based therapy is further supported by recent evidence assessing antipyretic efficacy in children. In a 2022 systematic review and meta-analysis of 108 trials involving 129,094 children, ibuprofen was among the most effective single-agent antipyretics, causing a rapid reduction in fever and with a safety profile similar to other agents investigated. This review did not directly compare dexibuprofen with ibuprofen. Still, it further supports the clinical utility of ibuprofen-based therapies for managing febrile illness in children and suggests a need for research on the active enantiomers (such as dexibuprofen) [16]. Below are some clinical implications of the present study. Controlling the fever can ease patient discomfort, promote oral intake, lower parental anxiety, and decrease unnecessary healthcare utilization. Dexibuprofen was effective in reducing body temperature when administered at 50% of the usual ibuprofen dose, suggesting it could be useful in routine pediatric practice. However, treatment should be individualized based on the child's clinical signs and symptoms, the underlying illness, hydration status, and contraindications to NSAID use [17]. This study has several limitations, however. This was done at a single tertiary center, with a relatively small number of patients and a fairly brief 4-hour follow-up period. There was no assessment of long-term clinical outcomes, recurrence of fever, adverse drug reactions, or caregiver satisfaction. In addition, the main paper did not provide any detailed statistics, such as confidence intervals for treatment effects. The comparative effectiveness and safety profile of dexibuprofen in the treatment of fevers in children warrants further randomized trials in larger populations, with longer follow-up and more complete safety monitoring, conducted across multiple centers [18].

Limitations

The study was conducted at a single tertiary care hospital with a limited number of patients (n = 150) and a short follow-up period (4 hours). The long-term antipyretic effect, incidence of recurrent fever, adverse drug reactions, and results by cause of fever were not assessed; therefore, it is difficult to generalize the results.

In febrile children, dexibuprofen also proved more effective as an antipyretic agent than conventional ibuprofen; it reduced body temperature at half the dose. The results indicate that dexibuprofen is an effective and well-tolerated drug for treating fever in children. These results should be validated with larger multicenter studies.

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