High performance liquid chromatography with UV detection for the simultaneous determination of sympathomimetic amines using 4-(4,5-diphenyl-1H-imidazole-2-yl)benzoyl chloride as a label. Operation for anorexigen-associated valvular heart disease. Ionamin online references

Ionamin online research references

mc.duke.edu

OBJECTIVE: This is a report of health-related quality of life (HRQOL) changes in obese patients completing at least 1 year of outpatient treatment in a weight reduction program combining phentermine-fenfluramine and dietary counseling. RESEARCH METHODS AND PROCEDURES: Participants were 141 women (87.6%) and 20 men (12.4%) who had an average body mass index at intake of 41.1 kg/m(2) (SD = 7.0, range = 29.5 to 67.0 kg/m(2)) and an average age of 44.9 years (SD = 9.3, range = 23 to 65 years). HRQOL was assessed at intake and at 1-year follow-up using the Impact of Weight on Quality of Life (IWQOL)-Lite questionnaire. The relationship between HRQOL changes and weight loss was examined using Pearson correlations. Clinically meaningful change in HRQOL was defined as a 1.96 SEM reduction in IWQOL-Lite total score. RESULTS: On average, participants lost 20.2 kg or 17.6% of their weight over the 1-year period. Of the participants, 15.5% lost <10% of their weight, 24.2% lost 10% to 14.9%, 23.6% lost 15% to 19.9%, and 36.6% lost 20% or more. All five IWQOL-Lite scales and total score showed statistically significant improvement over the 1-year period. Changes in IWQOL-Lite scores from intake to 1 year showed statistically significant correlations with percentage of weight loss for all subscales and total score. Subscale correlations with weight loss ranged from 0.166 (Public Distress) to 0.396 (Physical Function) and was 0.370 for the total score. Forty-four percent of participants losing <10% met the criterion of clinically meaningful change, compared with 51.3% losing 10% to 14.9%, 55.3% losing 15% to 19.95%, and 76.3% losing >20%. For total score and for three of the five IWQOL-Lite scales (Physical Function, Self-Esteem, and Sexual Life), the relationship between weight loss and clinically meaningful change was linear and was significant at p < 0.05. Physical Function and Self-Esteem were most strongly affected by weight loss. DISCUSSION: HRQOL changes, as measured by an obesity-specific instrument (IWQOL-Lite), are strongly related to weight reduction.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11557837&dopt=Abstract

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Biomed Chromatogr. 2001 Oct;15(6):379-88.
High performance liquid chromatography with UV detection for the simultaneous determination of sympathomimetic amines using 4-(4,5-diphenyl-1H-imidazole-2-yl)benzoyl chloride as a label.

Kaddoumi A, Kubota A, Nakashima MN, Takahashi M, Nakashima K.

Department of Analytical Research for Pharmacoinformatics, Graduate School of Pharmaceutical Sciences, Nagasaki University, Nagasaki, Japan.

A high performance liquid chromatographic method has been developed for the simultaneous determination of (+/-) fenfluramine (Fen) and phentermine (Phen) in addition to three other sympathomimetic amines-ephedrine (E), norephedrine (NE) and 2-phenylethylamine (2-PEA), using cyclohexylamine (CX) as an internal standard in plasma. The compounds were derivatized with 4-(4,5-diphenyl-1H-imidazole-2-yl)benzoyl chloride (DIB-Cl) to give the DIB-derivatives. The derivatives were then separated using an isocratic HPLC system with UV detection. The limits of detection for Fen, Phen, E, NE and 2-PEA in plasma ranged from 0.32 to 22.9 pmol on column at a signal-to-noise ratio of 3. The recoveries following alkaline extraction from plasma samples of known concentrations were found to be more than 94% for the studied compounds. This method might be useful for the screening of the studied sympathomimetic amines in human plasma samples in forensic as well as toxicological studies. Furthermore, the developed method was modified for the simultaneous determination of Fen and Phen in human and rat plasma using fluoxetine as an internal standard. The methods are reproducible and precise. Finally, the two drugs were administered intraperitoneally to rats in combination, and their plasma levels over the investigated time course were successfully determined. Copyright 2001 John Wiley & Sons, Ltd.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11559922&dopt=Abstract

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J Thorac Cardiovasc Surg. 2001 Oct;122(4):656-64.
Operation for anorexigen-associated valvular heart disease.

Caccitolo JA, Connolly HM, Rubenson DS, Orszulak TA, Schaff HV.

Division of Cardiovascular Surgery and Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.

OBJECTIVES: Recently, valvular regurgitation has been observed in patients who have taken fenfluramine or dexfenfluramine with or without phentermine. This study describes the clinical, echocardiographic, and pathologic findings of anorexigen-associated valvular heart disease and the surgical interventions required to treat it. METHODS: We reviewed clinical information on 14 patients with severe anorexigen-associated valvular disease who underwent cardiac operations. RESULTS: Thirteen women (mean age 44.2 +/- 5.3 years) received fenfluramine, 58.5 +/- 22.3 mg/day, and phentermine, 32.1 +/- 11.4 mg/day, for an average of 12.1 +/- 7.3 months before presentation. One woman received dexfenfluramine, 30 mg/day for 13 months, and phentermine, 60 mg/day, concomitantly for 6 months. Presenting symptoms included dyspnea (12 cases), palpitations (3), and atypical chest pain (3). Six patients had heart failure, and 4 had a new murmur. Echocardiography demonstrated severe mitral valve regurgitation in all patients. Seven also had aortic regurgitation, and 4 had significant tricuspid regurgitation. Four patients had successful mitral valve repair, 1 with concomitant aortic valve repair. Ten additional patients eventually required mitral valve replacement, 5 with concomitant aortic valve replacement. Excised valves demonstrated a glistening white appearance with plaque-like encasement of leaflets and chordae. Focal surface proliferation and fibrosis with a "stuck-on" appearance was consistently found. CONCLUSIONS: Anorexigen use may lead to severe multivalvular regurgitation with characteristic echocardiographic and pathologic findings. Recognition of drug-induced valvulopathy is important because of widespread use of these medications and the uncertain natural history of the disease. Early surgical experience suggests that valve repair is possible in these young patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11581595&dopt=Abstract

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