Efficacy of a Fixed-Dose Combination of Ibuprofen and Acetaminophen Compared With Individual Monocomponents in Adult Male Subjects With Endotoxin-Induced Fever: A Randomized Controlled Trial.

Purpose: This study evaluated antipyretic efficacy and onset of a novel fixed-dose combination (FDC) of ibuprofen (IBU; 250 mg) and acetaminophen (APAP; 500 mg) compared with placebo and IBU or APAP monocomponents. MET: This single-center, randomized, double-blind, placebo-controlled, full-factorial study was conducted in healthy males aged 18 to 55 years with pyrexia induced by intravenous administration of reference standard endotoxin (RSE). After attainment of an oral temperature ≥38.

Safety and tolerability of fixed-dose combinations of ibuprofen and acetaminophen: pooled analysis of phase 1-3 clinical trials.

Objectives: An ibuprofen (IBU)/acetaminophen (APAP) fixed-dose combination (FDC) for over-the-counter (OTC) use was developed with the goal of providing the same effective analgesic activity as full doses of the individual monocomponents, while reducing individual monocomponent drug exposures. Here, the safety and tolerability of the FDC is characterized using pooled safety data from phase 1-3 clinical trials in the FDC development program.

Methods: We conducted a pooled safety analysis of data from 7 clinical trials: three phase 1 pharmacokinetic trials, a phase 2 proof-of-concept trial, and three phase 3 trials (a single- and a multiple-dose trial in a dental pain model and a single-dose trial in an induced-fever model).

Evaluation of Fixed-Dose Combinations of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain: A Pilot, Dose-Ranging, Randomized Study.

Introduction: Ibuprofen and acetaminophen provide analgesia via different mechanisms of action and do not exhibit drug-drug interactions; therefore, combining low doses of each may provide greater efficacy without compromising safety.

Objectives: The present study assessed the analgesic efficacy of fixed-dose combinations (FDCs) of ibuprofen/acetaminophen (IBU/APAP) compared with ibuprofen 400 mg and placebo.

Methods: This 12-h, double-blind, proof-of-concept study compared three FDCs of IBU/APAP (200 mg/500 mg, 250 mg/500 mg, and 300 mg/500 mg) with ibuprofen 400 mg and placebo in patients with moderate-to-severe pain following third molar extraction.

Efficacy and Safety of Single and Multiple Doses of a Fixed-dose Combination of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain: Results From 2 Phase 3, Randomized, Parallel-group, Double-blind, Placebo-controlled Studies.

Objectives: A previous pilot study demonstrated that various fixed-dose combinations (FDCs) of ibuprofen (IBU) and acetaminophen (APAP) provided analgesic efficacy comparable to a higher dose of IBU, with the same safety profile. These studies further evaluated the chosen FDC IBU/APAP 250/500 mg formulation.

Materials And Methods: Two phase 3 dental pain studies enrolled healthy young patients with ≥moderate pain after ≥3 third molar extractions who received single-dose FDC IBU/APAP 250/500 mg, IBU 250 mg, APAP 650 mg, or placebo evaluated over 12 hours (study 1) or multiple-dose FDC or placebo every 8 hours, evaluated over 48 hours (study 2).

Phase I Pharmacokinetic Study of Fixed-Dose Combinations of Ibuprofen and Acetaminophen in Healthy Adult and Adolescent Populations.

Introduction: A fixed-dose combination (FDC) of ibuprofen and acetaminophen has been developed that provides greater analgesic efficacy than either agent alone at the same doses without increasing the risk for adverse events.

Methods: We report three clinical phase I studies designed to assess the pharmacokinetics (PK) of the FDC of ibuprofen/acetaminophen 250/500 mg (administered as two tablets of ibuprofen 125 mg/acetaminophen 250 mg) in comparison with its individual components administered alone or together, and to determine the effect of food on the PK of the FDC. Two studies in healthy adults aged 18-55 years used a crossover design in which subjects received a single dose of each treatment with a 2-day washout period between each.

Symptomatic treatment of dengue: should the NSAID contraindication be reconsidered?

Consensus guidelines for treatment of dengue fever from the World Health Organization and US Centers for Disease Control recommend acetaminophen to manage pain and fever but contraindicate nonsteroidal anti-inflammatory agents (NSAIDs) because of potentially increased bleeding risk, with thrombocytopenia as a complication. Neither acetaminophen nor ibuprofen (the NSAID with lowest bleeding risk) have been evaluated for dengue treatment in randomized, controlled clinical trials. Epidemiologic and cohort studies and case series describing NSAID use in dengue generally point to minimal or no significant increase in bleeding risk, except for aspirin.

Antipyretic Efficacy and Safety of Ibuprofen Versus Acetaminophen Suspension in Febrile Children: Results of 2 Randomized, Double-Blind, Single-Dose Studies.

Two blinded single-dose studies randomized children 6 months to 11 years old with fever to receive ibuprofen (IBU) pediatric suspension 7.5 mg/kg or acetaminophen (APAP) suspension 10 to 15 mg/kg. The primary efficacy parameter was time-weighted sum of temperature differences (TWSTD) from baseline through 8 hours for each study.

Onset of analgesia with ibuprofen sodium in tension-type headache: a randomized trial.

Background: Ibuprofen is known to be efficacious in the treatment of tension-type headache, the most common form of primary headache. A novel tablet formulation of ibuprofen sodium is more rapidly absorbed than standard ibuprofen. This study evaluated onset of analgesia and overall efficacy of ibuprofen sodium in episodic-type tension headache (ETTH) compared with standard ibuprofen and placebo.

Safety of a novel formulation of ibuprofen sodium compared with standard ibuprofen and placebo.

Background: Ibuprofen (IBU) is an efficacious over-the-counter analgesic/antipyretic with adverse event (AE) rates comparable to placebo. IBU sodium (IBU(Na)) is a newer, more soluble form that is absorbed faster than standard IBU, leading to more rapid analgesia. Although its safety and tolerability are expected to be comparable to standard IBU, this has not yet been reported.

Ibuprofen sodium is absorbed faster than standard Ibuprofen tablets: results of two open-label, randomized, crossover pharmacokinetic studies.

Background: A novel ibuprofen (IBU) formulation, Advil(®) Film-Coated Tablets (IBUNa), was developed.

Objective: Pharmacokinetic comparison of IBUNa versus other IBU formulations.

Study Design: Two randomized, single-dose, open-label, five-way crossover pharmacokinetic studies.

Onset of analgesia and efficacy of ibuprofen sodium in postsurgical dental pain: a randomized, placebo-controlled study versus standard ibuprofen.

Objectives: A novel, immediate-release tablet formulation of ibuprofen (IBU) sodium dihydrate, Advil Film Coated Tablets (IBUNa), has been developed that is absorbed faster than standard IBU tablets. The objective of the current study was to compare the efficacy and onset of analgesia of this new formulation with standard IBU tablets after a single dose.

Materials And Methods: Patients (N=316) with at least moderate baseline postsurgical dental pain were randomized to 400 mg IBUNa, Advil (IBUAdv), Motrin (IBUMot), or placebo.

Modeling the onset and offset of dental pain relief by ibuprofen.

Onset and offset of dental pain relief by ibuprofen following third molar extraction were modeled in a randomized, double-blind, placebo-controlled, parallel-group, 8-hour study of patients receiving either a novel effervescent ibuprofen tablet (400 mg; N = 30), standard ibuprofen tablets (Nurofen(®) 2 × 200 mg; N = 22), or placebo (N = 37). An Emax model was fit to pain relief scores. Linear hazard models were used to analyze the time to first perceptible relief (TFPR), the time to meaningful pain relief (TMPR), and time to remedication (REMD).

Children's ibuprofen suspension for the acute treatment of pediatric migraine.

Objective: To compare the efficacy of a single over-the-counter dose (7.5 mg/kg, p.o.

Spinal co-administration of cholecystokinin antagonists with morphine prevents the development of opioid tolerance.

The effects of intrathecal (i.t.) co-administration of the cholecystokinin (CCK) antagonists lorglumide or proglumide with a "low" (1 microgram) and "high" (10 micrograms) dose of i.

Opioid-monoamine interactions in spinal antinociception: evidence for serotonin but not norepinephrine reciprocity.

Anatomical and electrophysiological studies have demonstrated that enkephalinergic, noradrenergic, and serotonergic pathways projecting from the brain-stem to the dorsal horn inhibit nociceptive transmission at the spinal level. Previous attempts to delineate interactions between opioids, norepinephrine (NE), and serotonin (5-HT) in the production of spinal analgesia have produced conflicting results. The present study determined the effect of intrathecal (i.

Contrasting effects of acute vs. chronic tricyclic antidepressant treatment on central morphine analgesia.

Antinociception following central opioid microinjection in rats was assessed weekly via a tail-flick procedure during chronic tricyclic antidepressant (TCA) treatment. (1) Daily TCA: Subcutaneous injections of desipramine (DMI), 30 mg/kg, chlorimipramine (CMI), 10 mg/kg, or saline, 1 ml/kg, were given daily for 22 days. Morphine sulfate (M), 5 micrograms, was microinjected into the ventrolateral periaqueductal gray (VLPAG) at 7 day intervals.