Ibuprofen

Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species

CIDÁLIA PINA-VAZ*,†, FILIPE SANSONETTY†, ACÁCIO G. RODRIGUES*,†, J. MARTINEZ-DE-OLIVEIRA‡,  ANTÓNIO F. FONSECA* and PER-ANDERS MÅRDH§. Journal of Medical Microbiology September 2000 vol. 49 no. 9 831-840

Abstract

Ibuprofen, a non-steroidal anti-inflammatory drug, exhibited antimicrobial activity against Candida albicans and non-albicans strains. At 10 mg/ml, ibuprofen showed a rapid cidal activity against exponential growth phase C. albicans, accompanied by rapid and extensive leakage of intracellular K⁺, permeation to propidium iodide, lysis of spheroplasts and severe membrane ultrastructural alterations. These results indicate that the killing of Candida cells is due to direct damage to the cytoplasmic membrane. At 5 mg/ml, ibuprofen inhibited growth; however, it did not kill the yeasts and did not directly affect the cytoplasmic membrane. Evaluation of yeast metabolic vitality with the fluorescent probe FUN-1 showed that growth inhibition induced by the fungistatic drug concentration was due to metabolic alterations. The combination of ibuprofen with fluconazole resulted in synergic activity with eight of the 12 Candida strains studied, including four of the five fluconazole-resistant strains. The MICs of fluconazole for the fluconazole-resistant strains decreased 2–128-fold when the drug was associated with ibuprofen. When in combination with fluconazole, MICs for ibuprofen decreased by up to 64-fold for all the 12 strains studied. These results point to the practicability of using ibuprofen, alone or in combination with azoles, in the treatment of candidosis, particularly when applied topically, taking advantage of the drug’s antifungal and anti-inflammatory properties.

Topical or oral ibuprofen for chronic knee pain in older people. The TOIB study (full PDF)

Underwood M, Ashby D, Carnes D, Castelnuovo E, Cross P, Harding G, Hennessy E, Letley L, Martin J, Mt-Isa S, Parsons S, Spencer A, Vickers M,Whyte K. Health Technol Assess. 2008 May;12(22):iii-iv, ix-155.

Source

Centre for Health Sciences, Barts and The London, School of Medicine and Dentistry, Queen Mary University of London, UK.

Abstract

OBJECTIVES:

To determine whether GPs should advise their older patients with chronic knee pain to use topical or oral non-steroidal anti-inflammatory drugs (NSAIDs).

DESIGN:

An equivalence study was designed to compare the effect of advice to use preferentially oral or topical ibuprofen (an NSAID) on knee pain and disability, NSAID-related adverse effects and NHS/societal costs, using a randomised controlled trial (RCT) and a patient preference study (PPS). Reasons for patient preferences for topical or oral preparations, and attitudes to adverse effects, were explored in a qualitative study.

SETTING:

Twenty-six general practices in the UK.

PARTICIPANTS:

Participants comprised 585 people with knee pain, aged 50 years or over; 44% were male, mean age 64 years. The RCT had 282 participants: 144 in the oral group and 138 in the topical group. The PPS had 303 participants: 79 in the oral group and 224 in the topical group.

INTERVENTIONS:

Advice to use preferentially oral or topical NSAIDs for knee pain.

OUTCOME MEASURES:

The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures were the Short Form with 36 Items (SF-36), perceived troublesomeness of knee pain, satisfaction with health status, major adverse effects (unplanned hospital admissions and deaths) and minor adverse events over 12 months. The health economic analysis measured the comparative cost per quality-adjusted life-year (QALY) from both an NHS and a societal perspective over 1 and 2 years.

RESULTS:

Changes in the global WOMAC score at 12-months were equivalent in both studies: topical – oral, RCT difference=2 [95% confidence interval (CI) -2 to 6], PPS difference=1 (95% CI -4 to 6). There were no differences in the secondary outcomes, except for a suggestion, in the RCT, that those in the topical group were more likely to have more severe overall pain and disability as measured by the chronic pain grade, and more likely to report changing treatment because of inadequate pain relief. There were no differences in the rate of major adverse effects but some differences in the number of minor ones. In the RCT, 17% and 10% in the oral and the topical group, respectively, had a defined respiratory adverse effect (95% CI of difference -17% to -2.0%); after 12 months, the change in serum creatinine was 3.7 mmol/l (95% CI 0.9 to 6.5) less favourable in the oral than in the topical group, and 11% of those in the oral group reported changing treatment because of adverse effects compared with 1% in the topical group (p=0.02). None of these differences were seen in the PPS. Oral NSAIDs cost the NHS 191 pounds and 72 pounds more per participant over 1 year in the RCT and PPS respectively. In the RCT the cost per QALY in the oral group, from an NHS perspective, was in the range 9000-12,000 pounds. In the PPS it was 2564 pounds over 1 year, but over 2 years the oral route was more cost-effective. Patient preference for medication type was affected by previous experience of medication (including adverse reactions), other illness, pain elsewhere, anecdotes, convenience, severity of pain and perceived degree of degeneration. Lack of understanding about knee pain and the action of medication led to increased tolerance of symptoms. Potentially important symptoms may inadvertently have been disregarded, increasing participants’ risk of suffering a major adverse effect.

CONCLUSIONS:

Advice to use either oral or topical preparations has an equivalent effect on knee pain, but oral NSAIDs appear to produce more minor adverse effects than topical NSAIDs. Generally, these results support advising older people with knee pain to use topical rather than oral NSAIDS. However, for patients who prefer oral NSAID preparations rather than a topical NSAID, particularly those with more widespread or severe pain, the oral route is a reasonable treatment option, provided that patients are aware of the risks of potentially serious adverse effects from oral medication. Further research is needed into strategies to change prescribing behaviour and ensure that older patients are aware of the potential risks and benefits of using NSAIDs. Observational studies are needed to estimate rates of different predefined minor adverse effects associated with the use of oral NSAIDs in older people as are long-term studies of topical NSAIDs in those for whom oral NSAIDs are not appropriate.

Controversies and advances in non-steroidal anti-inflammatory drug (NSAID) analgesia in chronic pain management: Review (full PDF)

Premarketing surveillance of ibuprofen suppositories in febrile children

Hadas D, Youngster I, Cohen A, Leibovitch E, Shavit I, Erez I, Uziel Y, Berkovitch M. Clin Pediatr (Phila). 2011 Mar;50(3):196-9. doi: 10.1177/0009922810384847. Epub 2011 Jan 10.

Source

Division of Pediatrics and Clinical Pharmacology Unit, Assaf Harofeh Medical Center, Zerifin, Israel.

Abstract

In many countries, ibuprofen is available only in oral formulations. The authors aimed to investigate parental satisfaction and possible adverse reactions among children receiving newly marketed ibuprofen suppositories, prior to their arrival at the pharmaceutical points of distribution. Children needing antipyretic medication were recruited from 11 pediatric wards and clinics in Israel. Each patient received ibuprofen suppositories (5-10 mg/kg/dose) after completing a data collection form. After 3 to 7 days of treatment, information regarding parent satisfaction, possible adverse reactions, and concomitant use of drugs was obtained. Overall, 490 children completed the study. Parents’ satisfaction was high (4.5 ± 0.47 on a scale of 1-5), and 92.2% reported that they would use the medication in the future. Adverse reactions were reported in 8 patients (1.63%, 95% confidence interval = 1.77-3.25), the most common being diarrhea. Rectal administration of ibuprofen suppositories is well tolerated and overall satisfaction and the repeated expected use were high.

Oral versus rectal ibuprofen in healthy volunteers

Vilenchik R, Berkovitch M, Jossifoff A, Ben-Zvi Z, Kozer E. J Popul Ther Clin Pharmacol. 2012;19(2):e179-86. Epub 2012 May 16.

Source: Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel.

Abstract

OBJECTIVE: Ibuprofen is a safe and effective non steroidal anti-inflammatory drug (NSAID). Ibuprofen suppositories are marketed in Europe; but data regarding pharmacokinetics of rectal vs. oral ibuprofen in humans is scarce. The objective of this study is to compare the pharmacokinetics of single-dose rectal vs. oral ibuprofen in healthy adult volunteers.

METHODS: Ten healthy adult male volunteers, aged 20-37 years, received in a non-blind, cross-over setting, two formulations of ibuprofen. First, a 400 mg (about 5 mg/kg) of racemic ibuprofen suppository; second (after a three week washout period) the same dosage of ibuprofen syrup. Blood samples were collected before dosing and for 12 hours after administration. Pharmacokinetics analysis was preformed.

RESULTS: Mean peak plasma concentration (Cmax) of rectal ibuprofen was considerably lower, and the mean time to peak (Tmax) considerably longer, compared to oral ibuprofen. Absorption of rectal ibuprofen was considerably lower than oral ibuprofen, with a relative bioequivalence of 63%. Rectal ibuprofen reached therapeutic plasma concentration (>10 µg/ml) 45 minutes after dosing and remained in that range for four hours. The values of Vd/F and CL/F also differ significantly after rectal and oral administration, while no difference was found in the elimination rate constant (Kel) or half-life elimination (t1/2).

CONCLUSIONS: Racemic ibuprofen suppository has lower bioavailability compared with ibuprofen syrup. Therapeutic plasma concentrations of ibuprofen were reached 45 minutes after dosing and remained in that range for 4 hours. Ibuprofen suppositories can contribute to the management of fever and pain when the oral route is not available.

Back to Physicians Page

Back to Ingredients Page