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Biomedical subjects

F G McMahon

Publications and source records attributed to F G McMahon.

At least 19 recordsLinked to original sources
PubMed2002

Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors.

Sibutramine treatment in obesity results in significantly greater weight reduction compared with placebo, although weight loss with sibutramine may be accompanied by small but statistically significant mean increases in blood pressure (BP). This 52-week, placebo-controlled, double-blind, randomised study investigated the effects of sibutramine 20 mg once daily or placebo on body weight in 220 obese (body mass index (BMI) 27-40 kg/m2), hypertensive patients. At randomisation, hypertension was well controlled (< or = 95 mm Hg diastolic blood pressure (DBP)) with an angiotensin-converting enzyme (ACE) inhibitor, with or without concomitant thiazide diuretic therapy. Therapy for hypertension continued for the 52 weeks of the study. Sibutramine 20 mg produced significantly greater weight loss compared with placebo: 4.5 kg with sibutramine compared with 0.4 kg with placebo (last observation carried forward (LOCF); P < or = 0.05). A total of 62 patients (42.8%) treated with sibutramine lost < or = 5% of their body weight compared with six patients (8.3%) treated with placebo; 19 patients (13.1%) treated with sibutramine lost > or = 10% of their body weight compared with two patients (2.8%) treated with placebo (LOCF; P < or = 0.05 for both comparisons). Hypertension remained well controlled for the 52 weeks of the study with both sibutramine and placebo treatment. After 52 weeks, the differences between placebo treatment and sibutramine treatment for both mean supine systolic blood pressure (SBP) and DBP were approximately 3 mm Hg: mean DBP was 82.8 mm Hg with placebo treatment compared with 85.5 mm Hg with sibutramine treatment (LOCF; P = 0.004) and mean SBP was 130.4 mm Hg with placebo compared with 133.1 mm Hg with sibutramine (LOCF; P = 0.0497; both comparisons, sibutramine vs placebo). The mean increases in SBP and DBP did not appear to change the overall risk category for coronary heart disease end points. Changes in pulse rate at week 52 were a decrease of 0.3 beats per minute (bpm) for placebo treatment compared with an increase of 5.7 bpm for sibutramine treatment (P < 0.001). Mandated withdrawals from the study due to protocol-defined changes in BP were not statistically different between the two treatment groups. Greater favourable changes in lipid profile, serum glucose, and uric acid could be accounted for by greater weight losses occurring in the sibutramine treatment group. Sibutramine was well tolerated. This study indicates that in obese patients whose hypertension is well controlled at the outset with an ACE inhibitor, with or without concomitant thiazide diuretic therapy, sibutramine safely and effectively achieves weight loss without compromising good BP control.

Adult↗
PubMed2002

Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by beta-adrenergic blocking agents: a placebo-controlled, double-blind, randomised trial.

Sibutramine is a serotonin-noradrenaline reuptake inhibitor that is effective for long-term weight reduction and maintenance in obese patients when used as an adjunct to dietary and behavioural measures. Because the inhibition of noradrenaline reuptake may be expected to increase systolic and diastolic blood pressure (SBP and DBP) and pulse rate (PR), a 12-week multi-centre, placebo-controlled, double-blind study was designed to evaluate the efficacy and tolerability of sibutramine for weight loss in obese patients whose hypertension was well controlled (DBP < or = 95 mm Hg) by beta-adrenergic blocking agents (beta-blockers), with or without concomitant thiazide diuretics. Of the 61 patients randomised to sibutramine 20 mg once daily or placebo, 55 patients (90%) completed the study. After 12 weeks, sibutramine-treated patients lost significantly more weight than placebo-treated patients: mean weight reductions were 4.2 kg (4.5%) in the sibutramine group vs 0.3 kg (0.4%) in the placebo group (P<0.001). Greater weight reduction on sibutramine was accompanied by trends for greater mean reductions in serum triglycerides and very low density lipoprotein cholesterol. Sibutramine was well tolerated, and most adverse events were mild or moderate in severity. No sibutramine patient discontinued treatment because of an adverse event. Mean supine and standing DBP and SBP were not statistically significantly different between the sibutramine group and the placebo group at any post-baseline visit during the 12-week trial. At week 12, mean increases from baseline supine SBP and DBP, respectively, were 1.6 and 1.7 mm Hg for the sibutramine group vs increases of 0.4 and 1.3 mm Hg for the placebo group. At week 12, mean increases from baseline standing SBP and DBP, respectively, were 1.5 and 1.8 mm Hg for the sibutramine group vs an increase of 0.3 and a decrease of 0.8 mm Hg for the placebo group (P > 0.05 for treatment comparison). A statistically significant mean increase of 5.6 bpm (+/-8.25, s.d.) in supine PR from a baseline of 62 bpm was reported in sibutramine-treated patients at week 12, whereas placebo-treated patients had a mean supine PR decrease of 2.2 bpm (+/-6.43) (P < 0.001). In summary, sibutramine was well tolerated and effective in weight reduction. The addition of sibutramine did not result in an increase in BP in obese patients whose hypertension was well controlled by a beta-blocker. However, based on the potential for changes in BP and PR, obese patients being treated with sibutramine should be monitored periodically for changes in BP and PR and managed appropriately.

Adrenergic beta-Antagonists↗
PubMed2000

Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial.

BACKGROUND: Obesity is a highly prevalent medical condition and is commonly accompanied by hypertension. This study assessed the efficacy and safety of treatment with sibutramine hydrochloride for promoting and maintaining weight loss in obese patients with controlled hypertension, including a subset analysis of African American patients. PATIENTS AND METHODS: Obese patients with a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) between 27 and 40 and a history of hypertension controlled with a calcium channel blocker (with or without concomitant thiazide diuretic treatment) were randomized to receive sibutramine (n = 150) or placebo (n = 74) with minimal behavioral intervention for 52 weeks. African Americans constituted 36% of enrolled patients. Efficacy assessments were body weight and related parameters (BMI and waist and hip circumferences), metabolic parameters (serum levels of triglycerides, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol, glucose, and uric acid), and quality-of-life measures. Safety assessments included recording of blood pressure, pulse rate, adverse events, and reasons for discontinuation. RESULTS: For patients receiving sibutramine, weight loss occurred during the first 6 months of the trial and was maintained to the end of the 12-month treatment period. Among patients receiving sibutramine, 40.1% lost 5% or more of body weight (5% responders) and 13.4% lost 10% or more of body weight (10% responders) compared with 8.7% and 4.3% of patients in the placebo group, respectively (P<.05). Changes in body weight were similar among African Americans and whites. Sibutramine-induced weight loss was associated with significant improvements in serum levels of triglycerides, HDL-C, glucose, and uric acid. Waist circumference and quality-of-life measures also improved significantly in patients receiving sibutramine. Sibutramine-treated patients had small but statistically significant mean increases in diastolic blood pressure (2.0 mm Hg) and pulse rate (4.9 beats/min) compared with placebo-treated patients (-1.3 mm Hg and 0.0 beats/min; P<.05); these changes were similar among African Americans and whites. Most adverse events were mild to moderate in severity and transient. The most common adverse event resulting in discontinuation among patients receiving sibutramine was hypertension (5.3% of patients receiving sibutramine vs 1.4% of patients receiving placebo). CONCLUSIONS: In obese patients with controlled hypertension, sibutramine was an effective and well-tolerated treatment for weight loss and maintenance. Sibutramine-induced weight loss resulted in improvements in serum levels of triglycerides, HDL-C, uric acid, and glucose, and in waist circumference and quality-of-life measures. Blood pressure and heart rate increased by a small amount. Efficacy and safety profiles for sibutramine among African American and white obese patients with controlled hypertension were similar.

Adult↗
PubMed1999

Dose-related inflammatory effects of intravenous endotoxin in humans: evaluation of a new clinical lot of Escherichia coli O:113 endotoxin.

The administration of reference endotoxin (Escherichia coli O:113, Lot EC-5) to humans has been an important means to study inflammation in vivo; however, the supply of Lot EC-5 is depleted. A new lot of reference endotoxin (Clinical Center reference endotoxin [CCRE]), derived from the original bulk material extracted from E. coli O:113, was processed. The effects of 0-, 1-, 2-, and 4-ng/kg doses of intravenous CCRE and EC-5 were studied in 20 male subjects. CCRE resulted in dose-related increases in symptoms, temperature (P=. 016), total leukocyte count (P=.014), tumor necrosis factor-alpha (P=.004), interleukin (IL)-1 receptor antagonist (P=.004), IL-6 (P=. 005), IL-8 (P=.011), cortisol (P<.05), and C-reactive protein (P=. 04). These responses were attenuated (all P<.012) in subjects given Lot EC-5 (4 ng/kg) in comparison with those in subjects given CCRE, showing that, over several years, EC-5 had lost potency. Thus, in healthy subjects, the magnitude of exposure to CCRE results in a graded dose response of major components of innate immunity.

Adult↗
PubMed1998

Effects of an ACE inhibitor/calcium antagonist combination on proteinuria in diabetic nephropathy.

BACKGROUND: The degree of proteinuria in patients with diabetes correlates strongly with both an increase in progression of nephropathy as well as cardiovascular events. Moreover, post hoc analyses of recent clinical trials support the concept that reductions of blood pressure and proteinuria correlate with a slowed progression of nephropathy. Both angiotensin converting enzyme (ACE) inhibitors and the nondihydropyridine calcium antagonists, (non-DHPCAs) reduce both arterial pressure and proteinuria in those with diabetic nephropathy. METHODS: The present randomized, open label, parallel group designed study tests the hypothesis that, at similar levels of blood pressure, the combination of an ACE inhibitor, trandolapril (T) with the non-DHPCA, verapamil (V) produces a greater reduction in proteinuria over either agent alone at one year. Thirty-seven participants, mean age 59.6 +/- 5.8 years, with nephropathy (baseline creatinine 1.4 +/- 0.3 mg/dl and proteinuria of 1342 +/- 284 mg/dl) secondary to type 2 diabetes completed the study. Doses of drug were titrated in each group over eight weeks to achieve a goal blood pressure of < 140/90 mm Hg. All participants were counseled to ingest a sodium diet of < 120 mEq/day. RESULTS: Proteinuria reduction from baseline was significantly greater in the T+V group compared to either T alone (-33 +/- 8%, T vs. -62 +/- 10%, T+V; P < 0.001) or V alone (-27 +/- 8%, V vs. -62 +/- 10%, T+V; P < 0.001). No significant differences in either glomerular filtration rate, arterial pressure, fasting blood glucose or urinary sodium excretion were noted at one year. The mean daily dose of the individual components of T+V (2.9 +/- 0.8 mg, T/219 +/- 21.1 mg V) was significantly lower than the dose of either T alone 5.5 +/- 1.1 mg/day (P < 0.01) or V alone 314.8 +/- 46.3 mg, given in two divided doses (P < 0.01). CONCLUSION: These data support the concept that the combination of an ACE inhibitor with a non-DHPCA reduce proteinuria to a greater extent than either agent alone. This added antiproteinuric effect occurs at lower doses of each drug and is independent of further reductions in arterial pressure. These findings could have ramifications for slowing renal disease progression in patients with nephropathy from type 2 diabetes.

Aged↗
PubMed1997

Oxaprozin and piroxicam, nonsteroidal antiinflammatory drugs with long half-lives: effect of protein-binding differences on steady-state pharmacokinetics.

The nonsteroidal antiinflammatory drugs (NSAIDs) oxaprozin and piroxicam have long elimination half-lives (t 1/2 approximately 55 hours), permitting once-daily dose regimens. The protein-binding characteristics of these drugs, however, vary widely. This study examines the effect of these binding differences on the drugs' disposition kinetics at steady state. A total of 52 participants (26 young healthy volunteers, and 26 elderly osteoarthritic patients, 15 men and 37 women (2 of them poor metabolizers of debrisoquine [CYP2D6]) completed the two-period, two-treatment, randomized, single-dose and 21-day, once-daily multiple-dose, cross-over study. Doses of oxaprozin and piroxicam were 1,200 mg once daily and 20 mg once daily, respectively. Mean single-dose kinetic parameters of oxaprozin versus piroxicam did not differ more than +/-14% (t1/2, 53.0 versus 57.4 hours; apparent oral clearance adjusted for 70-kg body weight [Clpo], 0.139 versus 0.121 L/hr; apparent volume of distribution adjusted for 70-kg body weight [Vd/F]; 10.2 L versus 9.13 L). Protein binding was plasma-concentration dependent with oxaprozin (range, 10-400 mg/L) but not with piroxicam (range, 1-30 mg/ L). Steady-state conditions were established within 3 days with oxaprozin but took almost 12 days with piroxicam. Compared with the single-dose values, steady-state Clpo (Clpo,ss) and Vd/F of total drug increased with oxaprozin by almost 127% but remained within +/-10% with piroxicam. Post-steady-state apparent t 1/2 of the total and unbound drugs of approximately 62 hours were similarly prolonged with piroxicam but differed substantially with oxaprozin (50.6 hours [total drug] versus 23.8 hours [unbound drug]). Single dose Clpo (Clpo,sd) values of both NSAIDs were significantly correlated in the study populations. With both NSAIDs, Clpo in the two poor metabolizers of debrisoquine was within +/-20% of mean values for the population. Clinically important age- and gender-dependent decreases were not observed in the weight-adjusted, Clpo,sd or Vd/F values of the total drug for either NSAID. Clearances of the two NSAIDs were significantly correlated, suggesting that a common P450 isozyme (most likely CYP2C9, in that piroxicam is a known substrate of this isozyme) may be at least partly involved in the oxidative metabolism of these NSAIDs.

Adult↗
PubMed1995

Comparison of amlodipine and benazepril monotherapy to amlodipine plus benazepril in patients with systemic hypertension: a randomized, double-blind, placebo-controlled, parallel-group study. The Benazepril/Amlodipine Study Group.

A single-blind, run-in, randomized, double-blind, parallel-group, placebo-controlled comparison trial was conducted to assess the safety and efficacy of low-dose amlodipine 2.5 mg daily, low-dose benazepril 10 mg daily, and the combination of the two drugs at the same doses used once daily in patients (n = 401) with mild to moderate (stages I and II) systemic hypertension. Both monotherapy regimens were shown to significantly reduce both systolic and diastolic blood pressure compared with baseline placebo values, and the combination regimen was shown to be superior in lowering systolic and diastolic blood pressure when compared with either of the monotherapy regimens. The combination therapy also resulted in a greater percentage of patients having successful clinical response in mean sitting diastolic blood pressure. The amlodipine and benazepril regimen was also shown to be associated with a similar incidence of adverse experiences as the active monotherapy or placebo regimens, although the group given combination therapy appeared to have a lower incidence of edema than the group given amlodipine alone. Low-dose amlodipine (2.5 mg) plus benazepril (10 mg) provides greater blood-pressure-lowering efficacy than either monotherapy, and has an excellent safety profile.

Adult↗
PubMed1995

A multicenter comparison of adverse reaction profiles of isradipine and enalapril at equipotent doses in patients with essential hypertension.

A multicenter, randomized, double-blind trial compared the safety and efficacy of the dihydropyridine isradipine with the angiotensin-converting enzyme (ACE) inhibitor enalapril given twice daily for mild hypertension. 160 patients received either isradipine (starting at 1.25 mg twice daily) or enalapril (starting at 2.5 mg twice daily) for 10 weeks. The dosage was increased if the average sitting diastolic blood pressure was > 90 mm Hg. Significantly greater mean reductions in systolic blood pressure were seen after 2, 6, and 8 weeks of isradipine. However, by the end of the trial, 83% of patients receiving isradipine and 78% receiving enalapril showed a decrease of at least 5 mm Hg in sitting diastolic blood pressure to a level below 96 mm Hg. Possible or probable drug-related adverse effects were reported in 36% of patients showing a good antihypertensive response to isradipine, and in 30% of those who responded to enalapril. There was a trend for a lower frequency of adverse effects in isradipine non-responders (25%) and a higher frequency in enalapril non-responders (43%). Pruritus, dizziness, edema, and fatigue were reported more often with isradipine, and cough and changed bowel habits were more common with enalapril. The relationship between the pattern of adverse effects and the extent of blood pressure reduction may be dependent on the mechanism of action of a drug. In responders, isradipine and enalapril showed differing patterns, but a similar overall incidence of adverse effects.

Adolescent↗
PubMed1994

Placebos in medicine.

Explore the source record for details and available documents.

Controlled Clinical Trials as Topic↗
PubMed1994

Evaluation of the antipyretic effect of ketorolac, acetaminophen, and placebo in endotoxin-induced fever.

The authors studied the antipyretic effect of three intramuscular doses of ketorolac (15, 30, and 60 mg), acetaminophen 650 mg PO, and placebo in healthy male volunteers using an endotoxin-induced fever model. In this double-blind, double-dummy, parallel study, subjects were assigned randomly with equal probability to one of the above treatment groups. Thirty minutes after study medication administration, a 20 unit per kilogram dose of reference standard endotoxin (RSE) was administered intravenously, and temperature was determined every 15 minutes for an 8-hour period. Compared with placebo, all active treatment groups demonstrated a statistically significant reduction in both adjusted area under the temperature-by-time curve (AAUC) and the maximum increase over baseline temperature (dTmax). Furthermore, the 30 mg intramuscular dose of ketorolac demonstrated approximately the same antipyretic activity as the 650 mg oral dose of acetaminophen, and there was a statistically significant dose response across the three ketorolac doses studied (P < .0001). The majority of side effects reported during this study were symptoms associated with fever, including chills, headache, myalgia, and dizziness, all of which are effects of RSE. The frequency of side effects tended to be less in the treatment groups with the greatest antipyretic activity.

Acetaminophen↗
PubMed1993

A controlled study comparing the effects of nabumetone, ibuprofen, and ibuprofen plus misoprostol on the upper gastrointestinal tract mucosa.

BACKGROUND: This study was developed to compare the incidence of endoscopically diagnosed ulcers in elderly patients taking nabumetone, ibuprofen, or concomitant ibuprofen/misoprostol. Further research is indicated to better establish the clinical relevance of these endoscopy findings. METHODS: We conducted a prospective, multicenter, randomized, endoscopist-blinded, 12-week study involving 171 patients with osteoarthritis aged 60 years and older. Patients were randomized to receive nabumetone, 1000 mg (n = 58); ibuprofen, 600 mg four times daily (n = 53); or ibuprofen, 600 mg four times daily, administered concomitantly with misoprostol, 200 micrograms four times daily (n = 60). Endoscopy was performed at baseline and at weeks 2, 6, and 12. Endoscopy results were scored on a scale of 1 to 9. Significant ulcers were defined as breaks in the mucosa greater than 5 mm with appreciable depth. RESULTS: Of the 171 randomized patients, 148 completed the study. There was no significant difference in the incidence of significant ulcers between the nabumetone group and the ibuprofen/misoprostol group (one vs zero). There were significantly fewer significant ulcers in the nabumetone and ibuprofen/misoprostol groups than in the ibuprofen monotherapy group (one and zero vs eight; P < .01). There also was a significant difference in the time to ulcer development, with a greater risk of developing an ulcer sooner with ibuprofen treatment (P < .01) than either nabumetone or ibuprofen/misoprostol treatment. The severity of osteoarthritis, based on physicians' assessments, improved in 64% of patients in the nabumetone group, 55% of those in the ibuprofen group, and 63% of those in the ibuprofen/misoprostol group. CONCLUSIONS: Nabumetone is equivalent in ulcerogenicity to concomitant ibuprofen/misoprostol and is significantly less ulcerogenic than ibuprofen alone.

Aged↗
PubMed1993

Can garlic reduce levels of serum lipids? A controlled clinical study.

PURPOSE: To assess the effects of standardized garlic powder tablets on serum lipids and lipoproteins, glucose, and blood pressure. SUBJECTS AND METHODS: Forty-two healthy adults (19 men, 23 women), mean age of 52 +/- 12 years, with a serum total cholesterol (TC) level of greater than or equal to 220 mg/dL received, in a randomized, double-blind fashion, either 300 mg three times a day of standardized garlic powder in tablet form or placebo. Diets and physical activity were unchanged. This study was conducted in an outpatient, clinical research unit. RESULTS: The baseline serum TC level of 262 +/- 34 mg/dL was reduced to 247 +/- 40 mg/dL (p < 0.01) after 12 weeks of standard garlic treatment. Corresponding values for placebo were 276 +/- 34 mg/dL before and 274 +/- 29 mg/dL after placebo treatment. Low-density lipoprotein cholesterol (LDL-C) was reduced by 11% by garlic treatment and 3% by placebo (p < 0.05). There were no significant changes in high-density lipoprotein cholesterol, triglycerides, serum glucose, blood pressure, and other monitored parameters. CONCLUSIONS: Treatment with standardized garlic 900 mg/d produced a significantly greater reduction in serum TC and LDL-C than placebo. The garlic formulation was well tolerated without any odor problems.

Adult↗
PubMed1993

Cholesterol levels in 1,084 healthy New Orleans males.

It is widely recognized that elevated cholesterol levels constitute a major risk factor for the development of atherosclerosis and coronary heart disease. Most of the previous surveys conducted in an effort to learn more about incidence of hypercholesterolemia involved patients who had other concurrent risk factors such as hypertension, obesity, diabetes mellitus, cigarette smoking, or a history of myocardial infarction. Relatively few studies have been conducted in younger populations or in healthy individuals. Because we had access to baseline cholesterol data on 1,084 relatively young, otherwise completely healthy, nonobese males, we elected to determine the prevalence of hypercholesterolemia in this population. Elevated cholesterol levels (> 200 mg/dL) were found in 25.2% of our healthy subjects. These findings help to confirm the presence of a potentially serious public health problem existing among otherwise healthy, relatively young men in our community.

Adult↗
PubMed1992

Safety and pharmacokinetics of multiple doses of intravenous ofloxacin in healthy volunteers.

The safety and pharmacokinetics of ofloxacin in 48 healthy male volunteers were studied in a two-center, randomized, double-blind, placebo-controlled study. Ofloxacin (200 or 400 mg) or placebo was administered as 1-h infusions every 12 h for 7 days. Plasma ofloxacin concentrations were measured by high-performance liquid chromatography. Mean harmonic half-lives ranged from 4.28 to 4.98 h in the 200-mg dosing group and from 5.06 to 6.67 h in the 400-mg dosing group. Intragroup comparisons of trough plasma concentration-versus-time data from study days 2 through 7 revealed that steady state was achieved by day 2 of both multiple-dose regimens. Intergroup comparisons of mean harmonic half-lives, the areas under the concentration-time curve from 0 to 12 and 0 to 60 h, clearance, and apparent volume of distribution (area method) revealed that the pharmacokinetics of ofloxacin are dose independent. Both ofloxacin dosage regimens appeared to be reasonably well tolerated. The two dosage regimens of ofloxacin, 200 or 400 mg every 12 h, appear to be safe and provide serum drug concentrations in excess of the MICs for most susceptible pathogens over the entire dosing interval.

Adolescent↗
PubMed1991

A new clinical bioassay for antipyresis.

Three studies that describe antipyretic bioassay are detailed. Reference Standard Endotoxin (RSE) was used to induce fever in healthy male volunteers under randomized, single-dose, double-blind, parallel, and standard drug-control conditions. Thirty minutes before administering RSE, the subjects were medicated with test drug, and oral temperatures were recorded every 15 minutes for 6 to 8 hours. Two NSAIDs and a centrally acting analgesic were evaluated. Both doses of a propionic derivative, three high doses of tebufelone (a new NSAID), as well as the high dose of flupirtine effectively obtunded the fever response to RSE. Adverse reactions consisting of flu-like symptoms such as myalgia, headache, and chills were also significantly reduced with the standard as well as test drugs. The authors conclude that the RSE model is a quick, safe, and reliable method to evaluate antipyresis and to predict other pharmacologic effects of these types of drugs, such as analgesia.

Adult↗
PubMed1991

Antipyretic activity of tebufelone (NE-11740) in man.

Tebufelone (formerly NE-11740) is a member of the new class of di-tert-butyl-phenol anti-inflammatory agents. It has previously been reported that this new agent has potent analgesic, antipyretic, and anti-inflammatory effects using in vitro, in vivo, and ex vivo experimental models. A randomized, active- and placebo- controlled double-blinded study in 120 healthy males, 20 to 55 years old, was conducted to clinically assess tebufelone's antipyretic activity. Subjects received a single peroral dose of placebo, 650 mg aspirin (ASA), or tebufelone at doses of 25, 50, 100, or 200 mg. Thirty minutes later, E. coli endotoxin (2 ng/kg) was administered intravenously. Oral temperatures were recorded at 15 minute intervals from 30 minutes post dosing to 8 hours post endotoxin administration. Areas under the temperature curves (AUCs), adjusted for baseline, were significantly lower than placebo for ASA and all but the 25 mg tebufelone groups. An AUC dose-response equation estimates 60 mg tebufelone as equivalent to 650 mg ASA, with 50 mg tebufelone not significantly greater than 650 mg ASA. Side effects, attributable to the endotoxin, included mild flu-like symptoms and were worse in the placebo group and the non-efficacious 25 mg tebufelone group. Doses of 100 and 200 mg tebufelone had onset characteristics indistinguishable from 650 mg ASA, whereas 50 mg tebufelone showed significantly slower onset while suppressing temperature for a longer period than ASA. These results provide an important early demonstration of tebufelone's biological activity in man.

Adult↗