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Paediatrica Indonesiana, Vol. 45, No. 9-10 • September - October 2005 • 211
Paediatrica Indonesiana
VOLUME 45 NUMBER 9-10September - October • 2005
Original Article
From the Department of Child Health, Medical School, University of
Indonesia, Jakarta, Indonesia.
Reprint requests to: Sri Rezeki S Hadinegoro, MD, PhD, Infection
and Tropical Medicine Division, Department of Child Health, Medical
School, University of Indonesia, Cipto Mangunkusumo Hospital, Jl.
Salemba No. 6, Jakarta, Indonesia. Tel. 62-21-3918301; Fax. 62-21-
3907743
The efficacy of suppository versus oral ibuprofen for
reducing fever in children
Suhesti Handayani, MD; Sri Rezeki Hadinegoro MD, PhD;
Sudigdo Sastroasmoro, MD, PhD
of prostaglandin by the hypothalamic temperature
setting point. A non-steroidal antipyretic agent can
reduce prostaglandin synthesis by blocking the
cyclooxygenase enzyme.1,2
Ibuprofen [2-(4-isobutylphenyl) propionic acid]
is effective for reducing prostaglandin biosynthesis,
besides having analgesic, antipyretic, and anti-in-
flammatory effects. In the United States, ibuprofen
tablets have been approved for adults and children
over 12 years old as a nonprescribed antipyretic drug
since 1984. Recently, ibuprofen syrup and tablets
have been approved for younger children.3
The administration of antipyretics might cause
some problems, since children may not be able or
refuse to take it, may throw it up, may be suffering
from convulsions, or may be under sedation. In such
cases, an ibuprofen suppository can be an alterna-
tive solution.4-6
As of today, there has been no study comparing
the effectiveness of ibuprofen suppository to that of oral
ibuprofen in Indonesian children. The objective of this
study was to compare the antipyretic efficacy of oral
ibuprofen to that of the suppository preparation.
Fever is the increase of body temperature beyond
the normal circadian range, induced by
endogenous pyrogens which trigger the release
ABSTRACT
Background Ibuprofen suppository is used to reduce fever in
children who are unable to receive it orally. The effectiveness of
ibuprofen suppository compared to that of oral ibuprofen has not
been documented in Indonesian children.
Objective The aim of this study was to compare the efficacy of
ibuprofen suppository with that of oral ibuprofen for reducing
fever in children.
Methods This study was a randomized clinical trial without blind-
ing on children aged 2-5 years with body weight of 12.5 to 16 kg
who had fever. Subjects received ibuprofen in either oral (7.5
mg/kg) or suppository (125 mg) form. The temperature was mea-
sured prior to ibuprofen administration, 30 minutes afterwards,
and every subsequent half hour until the end of the sixth hour.
Any observed adverse effects were recorded.
Results Mean time needed for fever reduction was 2.72 (SD 1.1)
hours in the suppository group, compared to 3.43 (SD 0.9) hours
in the oral group (P=0.004). The mean rate of fever reduction in
the suppository group was 0.90 (SD 0.4) °C/hour, while in the
oral group it was 0.61 (SD 0.3) °C/hour. However, mean maxi-
mum temperature lowering ability did not differ significantly [2.11
(SD 0.7) °C for the suppository group and 1.99 (SD 0.7) °C, for
the oral group (P=0.489)]. There was no significant difference in
mean duration of effect [220.8 (SD 83.0) hours for the supposi-
tory group and 196.6 (SD 92.7) hours for the oral group (p=0.231)].
Conclusions There was no significant difference between both
preparations in maximum temperature lowering ability and dura-
tion of effect. Temperature reduction was significantly faster
with the administration of ibuprofen suppository [Pediatr
Indones 2005;45:211-216].
Keywords: fever, ibuprofen, children
Paediatrica Indonesiana
212 • Paediatrica Indonesiana, Vol. 45, No. 9-10 • September - October 2005
Methods
This study was an open, randomized clinical trial
conducted at the outpatient clinic, Department of
Child Health, Medical School, University of
Indonesia, Cipto Mangunkusumo Hospital, Jakarta
from March 1, 2003 until March 31, 2004. Prior
approval was obtained from the Ethical Committee
of the Medical School, University of Indonesia.
Studied subjects were children suffering from
fever for 7 days or less with a body temperature of
38.5-40°C, aged 24-60 months, with normal body
weight (10th-90th percentile on the NCHS curve)
between 12.5-16 kg, without edema. Parental con-
sent was obtained for all subjects. The subjects had
not taken fever reducing medication for the past 6
hours (the previous night), had not taken corticos-
teroids for at least a week prior to the study, and
had not used a fever reducing compress for the past
4 hours. Exclusion criteria were history of convul-
sion triggered by fever, allergy to ibuprofen or any
other non-steroidal analgesic drug, asthma, gastri-
tis, ear infection/auditory canal anatomical defects,
cardiac or renal failure, receiving anticoagulant
medication, and dehydration.
Subjects who met the inclusion criteria were
randomly divided into two groups; group A received
oral ibuprofen and group B received ibuprofen sup-
pository. A commercially available ibuprofen prepa-
ration (Proris®) was used. The oral dose was 7.5
mg/kg in powder form and the suppository dose was
125 mg. Immediately before administering the drug,
the first temperature reading (H0) was taken. Fol-
lowing drug administration, subjects were placed
in an observation room for 6 hours. Subsequent tem-
perature readings were taken every half hour until
the end of the 6th hour (H6). Temperature readings
and adverse effects were recorded by medical per-
sonnel. Subjects who developed hyperpyrexia (tem-
perature of >40°C) during the observation period were
dropped out from the study and treated accordingly.
Body temperature readings were taken using an in-
frared ear thermometer (Braun IRT 3020).
The variables used to compare the efficacy of
the two forms of medication were Wmax, δt°, K (δt°/
Wmax), the duration for which the body tempera-
ture was kept <38.5°C, and the proportion of sub-
jects who reached a body temperature of less than
38.5°C within the observation period. Wmax was the
time in hours needed to reach the lowest possible
body temperature during the observation period. δt°
was the difference in body temperature in °C be-
tween the first reading (H0) and the lowest body
temperature reached within the observation period.
K (δt°/ Wmax) was the rate of body temperature
reduction; this was determined by dividing δt° by
Wmax, expressed in oC/hour. The Student’s inde-
pendent t-test was used to analyze data with nor-
mal distribution. Data with skewed distribution
were analyzed using the Mann-Whitney rank test.
Results
Eighty children, forty in each group were enrolled
as studied subjects. Five subjects dropped out; 2
(one from each group) due to hyperpyrexia, 1 from
the oral group due to non-compliance with the study
protocol), and 2 (one from each group) did not
complete the 6-hour observation period. Finally, 75
subjects were analyzed. Subjects’ characteristics are
shown in Table 1.
TABLE 1. SUBJECTS CHARACTERISTICS
Characteristics Mean (SD)
Oral group Suppository group
n=36 n=39
Age (years) 3.00 (0.7) 3.42 (0.9)
Body weight (kg) 13.25 (1.7) 13.88 (2.1)
Pre-treatment body temperature (oC) 39.04 (0.5) 39.18 (0.5)
Length of fever (days) 3 (1 – 14)* 2 (0.5 – 14)*
Dosage (mg/kg body weight) 7.77 (0.8) 9.20 (1.3)
* Mean (range)
Paediatrica Indonesiana, Vol. 45, No. 9-10 • September - October 2005 • 213
Suhesti Handayani et al: Efficacy of suppository versus oral ibuprofen
The cause of fever was mostly viral infection,
such as ARI (acute respiratory tract infection), di-
arrhea, common cold, dengue, chickenpox, mumps,
and hepatitis.
Results of body temperature monitoring
(Figure 1) show that both groups had reduced
fever below 38.5°C in the first hour. In the sec-
ond hour a significant difference of body tem-
perature reduction was observed, with the sup-
pository group being able to reduce body tem-
perature to a further extent than the oral group
[mean temperature 37.54 (SD 0.6) °C vs. 37.87
(SD 0.7) °C (P=0.033)]. The mean lowest body
temperature reached by the suppository group
was 37.40 (SD 0.6) °C, 2.5 hours after the first
observation, while that reached by the oral group
was 37.50 (SD 0.8) °C during the 3rd hour. The
following rise of body temperature did not differ
significantly between the two groups, and both
groups returned to a body temperature of 38.5°C
at the 6th hour.
Comparison of the efficacy of oral and supposi-
tory ibuprofen is shown in Table 2. The suppository
reached the lowest body temperature significantly
faster than oral ibuprofen [2.72 (SD 1.1) hours vs.
3.43 (SD 0.5) hours (P=0.05)], with a mean differ-
ence of 0.71 hours or 40 minutes. The mean rate of
body temperature reduction (δt°/Wmax) was 0.90
(SD 0.4) °C/hour for the suppository and 0.61 (SD
0.3) °C/hour for oral ibuprofen (P=0.001). How-
ever, the lowest body temperature reached and the
duration for which body temperature was kept be-
low 38.5°C did not differ significantly. The body
temperature of one subject from the oral group did
not drop to below 38.5°C, so the duration of effec-
tiveness was conducted on 74 subjects only.
During the six-hour observation period, one
subject from the oral group was recorded to throw
up twice. No special treatment was given and no
further incident occurred after the parents stopped
administering ibuprofen during the 24-hour home
observation.
FIGURE 1. BODY TEMPERATURE PATTERN DURING THE OBSERVATION PERIOD
TABLE 2.COMPARISON OF THE EFFICACY OF ORAL AND SUPPOSITORY IBUPROFEN
Outcome measure Mean (SD) P
Oral group Suppository group
n=36 n=39
The lowest body temperature reached (oC) 37.05 (0.6) 37.08 (0.6) 0.839
Wmax (hours) 3.43 (0.9) 2.72 (1.1) 0.004
δto (oC) 1.99 (0.7) 2.11 (0.7) 0.489
δto/Wmax (oC/hour) 0.61 (0.3) 0.90 (0.4) 0.001
Effective duration (minutes) 196.6 (92.7) 220.8 (83.0) 0.231
Mean body temperature (oC)
Paediatrica Indonesiana
214 • Paediatrica Indonesiana, Vol. 45, No. 9-10 • September - October 2005
Discussion
One possible explanation for the significant
differences between both groups was the relatively
higher dose of ibuprofen suppository. We could not
administer a suppository dose equivalent to the oral
dose since it was impossible to cut the suppository
into parts. However, a study conducted by Kelley3
showed that a significant difference only occurred
at a dose of 5 mg/kg body weight but not at 10 mg/
kg body weight.
Age, ranging from 2-5 years, was selected to
avoid side effects that might occur in very young
children (under 2 years old), although according to
Mc Intyre et al7 ibuprofen is safe for infants as young
as 2 months old. Eventhough the mean age of sub-
jects in both age groups were different (3 years old
in the oral group and 3.4 years old in the supposi-
tory group); it had no clinical relevance since both
groups had similar anatomical and physiological
conditions. The American Hospital Formulary Ser-
vice (AFHS) medicine guide also states that there
is no pharmacological difference in administering
ibuprofen to children aged 2-11 years.8 A study by
Kaufmann also found that age does not significantly
affect absorption, elimination rate, or drug concen-
tration. Different pharmacokinetics in younger chil-
dren is caused by the difference in body surface
area.9
The pre-treatment body temperature did not
differ significantly between the groups (39.04°C vs.
39.18°C). This is a very important finding, consider-
ing the fact that δt° or the difference between the
pre-treatment and the lowest body temperature is
one of the parameters for drug efficacy.
Most of the subjects were diagnosed as viral
acute respiratory tract infection. This supports the
inclusion criteria in limiting the length of the fever
to less than 7 days, to guarantee that the fever was
the one caused by infection instead of any other
inflammatory disease.
According to AFHS, the peak plasma con-
centration of ibuprofen in plasma is reached at 1-2
hours.8 Mc Intyre et al,7 who compared oral
ibuprofen 7.5-10 mg/kg to paracetamol of various
dosages, has shown that the lowest body tempera-
ture was reached in the 3rd hour. However, Kelley,3
Walson PD,10 Amdekar,11 and Kauffmann9 reported
that the lowest body temperature was reached be-
tween the 3rd and 4th hour. Kauffmann9 and Kelley3
reported that the maximum level reached after oral
administration was at 40 minutes and 60±19.7
minutes respectively. The above findings show
that there is a gap between the time when the
maximum plasma ibuprofen concentration is
reached and that when the clinical antipyretic ef-
fect can be detected. The time needed by oral and
suppository ibuprofen to reduce body temperature
to the lowest point has a statistically significant
difference with a mean difference of 40 minutes
(0.71 hours). This finding does not concur with
that of an earlier study by the Pharmacology De-
partment, Medical School, University of Gadjah
Mada, which stated that the maximum level of
ibuprofen in blood after administering a supposi-
tory to adult volunteers was reached in the 2nd hour,
and took significantly longer than the oral treat-
ment (40 minutes).12 The study by Maunuksela
showed that in the 2nd hour, there are also reduc-
tions of pain and heart rate after administering an
Ibuprofen suppository to children post-operatively.13
The rate of body temperature reduction, which is
measured as the degree of body temperature dif-
ference divided by the time it takes to reach the
lowest body temperature (δt°/Wmax), was in ac-
cordance with the above results, with the supposi-
tory group being slightly faster than the oral group
(0.9°C/hour vs. 0.6oC/hour, P= 0.001). The re-
duction of body temperature from the pre-treat-
ment level to the lowest point showed no signifi-
cant difference (1.99°C for the oral group and
2.11°C for the suppository group, P=0.489). The
findings for the oral group did not differ greatly
from other oral ibuprofen studies.7,10,14 The effec-
tive duration for which body temperature was main-
tained below 38.5°C showed no significant differ-
ence between both preparations (196.6 minutes for
the oral group and 220.8 minutes for the supposi-
tory group, P=0.231). This concurs with the ref-
erences which state that ibuprofen will reduce body
temperature for 3-4 hours.8,15,16 Research by Gianni
et al17 showed that this duration was 3.79 hours. In
our study, however, one subject never reached a
body temperature below 38.5°C.
The slower absorption rate for oral ibuprofen is
expected because the drug must be absorbed intes-
Paediatrica Indonesiana, Vol. 45, No. 9-10 • September - October 2005 • 215
Suhesti Handayani et al: Efficacy of suppository versus oral ibuprofen
tinally, transported through the liver into the blood
circulation. The same process will happen if sup-
pository drugs are mostly absorbed by the superior or
median hemorrhoid veins that go into the vena porta
and perhaps even slower because the rectum’s mu-
cosa has a smaller surface area than the intestinal
mucosa.5,18 However, if the suppository drug is ab-
sorbed mostly in the lower rectum, which is served
by the inferior hemorrhoid vein, the drug will enter
the inferior vena cava and produce a faster systemic
reaction.18
The most frequent side-effect of ibuprofen as
other non-steroid analgesic inflammatory drugs
(NSAID), is gastrointestinal disturbance. However,
this side effect is mostly well tolerated.8,16 Five to
fifteen percent of patients who receive ibuprofen will
have this side effect, although it is less likely to hap-
pen than when using aspirin.16 Side effects mostly
occur in overdose conditions (intentionally or oth-
erwise) or long term, for example, in use as an anal-
gesic for rheumatism or other collagen diseases.19,20
Other studies comparing oral ibuprofen with oral
aspirin in long term use (2 weeks) have recorded
gastrointestinal side effects.17 Mc Intyre et al., who
administered multiple dosages of ibuprofen in their
study, found that six out of 77 patients suffered from
vomiting, abdominal discomfort, and urticaria.7
Other studies which used a single dose of ibuprofen
found that only one out of 64 subjects suffered from
abdominal discomfort.3
It can be concluded that the efficacy of
ibuprofen suppository is equal to that of oral
ibuprofen, with the suppository resulting in a faster
response.
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