-
American Journal of Therapeutics Jul 2011Phentermine is the most widely used antiobesity drug in the United States. Although no evidence of phentermine addiction has been published, fear that phentermine has...
Phentermine is the most widely used antiobesity drug in the United States. Although no evidence of phentermine addiction has been published, fear that phentermine has addiction potential has contributed to curtailment of its worldwide use in clinical practice. The aim of this study was to evaluate the abuse and addiction potential of long-term phentermine pharmacotherapy in patients in a weight management program. Thirty-five patients in a weight management program who abruptly stopped taking prescribed phentermine on their own initiative were examined using the 18-item Kampman Cocaine Selective Severity Assessment scale modified for phentermine. The Kampman Cocaine Selective Severity Assessment scale has also been modified by McGregor for amphetamines to assess withdrawal from amphetamine in amphetamine-addicted subjects. For comparison, 35 new patients were examined with the same scale before any treatment was initiated. Data from the treated and untreated groups were compared by t test with each other and with published data from amphetamine-addicted subjects. There were no significant differences in individual items or total scores between the patients who stopped phentermine abruptly and the patients who had never taken phentermine. There was a striking and significant difference in individual and total scores between the phentermine-treated subjects and the amphetamine-dependent subjects. Cravings for the substance abused, the hallmark characteristic of substance dependence and withdrawal, were entirely absent in the phentermine-treated subjects. Abrupt cessation of long-term phentermine therapy does not induce amphetamine-like withdrawal. Long-term phentermine therapy does not induce phentermine cravings. Symptoms observed after abrupt phentermine cessation represent loss of therapeutic effect and are not withdrawal.
Topics: Adult; Appetite Depressants; Female; Humans; Male; Middle Aged; Obesity; Phentermine; Substance Withdrawal Syndrome; Surveys and Questionnaires; Treatment Refusal; Withholding Treatment
PubMed: 20592662
DOI: 10.1097/MJT.0b013e3181d070d7 -
The Neurologist Apr 2015
Topics: Encephalitis; Female; Humans; Intracranial Hemorrhages; Phentermine
PubMed: 25888200
DOI: 10.1097/NRL.0000000000000022 -
Psychopharmacology Jun 2015Synergistic or supra-additive interactions between the anorectics (dex)fenfluramine and phentermine have been reported previously in the rat and in the clinic. Studies... (Comparative Study)
Comparative Study
RATIONALE
Synergistic or supra-additive interactions between the anorectics (dex)fenfluramine and phentermine have been reported previously in the rat and in the clinic. Studies with 5-HT2C antagonists and 5-HT2C knockouts have demonstrated dexfenfluramine hypophagia in the rodent to be mediated by actions at the 5-HT2C receptor. Given the recent FDA approval of the selective 5-HT2C agonist lorcaserin (BELVIQ®) for weight management, we investigated the interaction between phentermine and 5-HT2C agonists on food intake.
OBJECTIVES
This study aims to confirm dexfenfluramine-phentermine (dex-phen) synergy in a rat food intake assay, to extend these findings to other 5-HT2C agonists, and to determine whether pharmacokinetic interactions could explain synergistic findings with particular drug combinations.
METHODS
Isobolographic analyses were performed in which phentermine was paired with either dexfenfluramine, the 5-HT2C agonist AR630, or the 5-HT2C agonist lorcaserin, and inhibition of food intake measured in the rat. Subsequent studies assessed these same phentermine-drug pair combinations spanning both the full effect range and a range of fixed ratio drug combinations. Satellite groups received single doses of each drug either alone or in combination with phentermine, and free brain concentrations were measured.
RESULTS
Dex-phen synergy was confirmed in the rat and extended to the 5-HT2C agonist AR630. In contrast, although some synergistic interactions between lorcaserin and phentermine were observed, these combinations were largely additive. Synergistic interactions between phentermine and dexfenfluramine or AR630 were accompanied by combination-induced increases in brain levels of phentermine.
CONCLUSIONS
Dex-phen synergy in the rat is caused by a pharmacokinetic interaction, resulting in increased central concentrations of phentermine.
Topics: Animals; Appetite Depressants; Dexfenfluramine; Drug Synergism; Eating; Fenfluramine; Male; Phentermine; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT2 Receptor Agonists
PubMed: 25524140
DOI: 10.1007/s00213-014-3829-2 -
Expert Opinion on Drug Metabolism &... 2023DWP16001, a sodium-glucose cotransporter-2 inhibitor, has shown promise for improving blood glucose control and facilitating weight loss. Co-administration with... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
DWP16001, a sodium-glucose cotransporter-2 inhibitor, has shown promise for improving blood glucose control and facilitating weight loss. Co-administration with phentermine could enhance these effects. So, we aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) interactions of DWP16001 and phentermine.
METHODS
We conducted a randomized, open-label, 3-treatment, 6-sequence, 3-period crossover study involving 24 healthy adults. Participants received either DWP16001 (2 mg), phentermine (37.5 mg), or a combination of both once daily for 7 days. Blood samples, urine samples, and body weights were collected to evaluate the PK and PD.
RESULTS
The PK of the combination was found to be similar to that of the monotherapy. The geometric mean ratio (GMR) of C, and AUC were 0.98 and 1.00, respectively, for DWP16001, and 1.01 and 0.94, respectively, for phentermine. Co-administration did not significantly affect the 24-hour urinary glucose excretion compared to DWP16001 monotherapy, and the GMR was 0.90. Participants tended to experience greater weight loss in the combination therapy group, and all demonstrated good tolerance.
CONCLUSIONS
Our findings indicate that there were no significant interactions during co-administration. These results suggest that the combination of DWP16001 and phentermine may be safe and effective for the treatment of obesity and diabetes.
CLINICAL TRIAL REGISTRATION
NCT05321732.
Topics: Adult; Humans; Sodium-Glucose Transporter 2 Inhibitors; Healthy Volunteers; Phentermine; Cross-Over Studies; Area Under Curve; Glucose; Weight Loss; Sodium; Drug Interactions
PubMed: 37593838
DOI: 10.1080/17425255.2023.2249397 -
The New England Journal of Medicine Aug 1997
Topics: Appetite Depressants; Drug Combinations; Female; Fenfluramine; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Obesity; Phentermine
PubMed: 9271487
DOI: 10.1056/NEJM199708283370909 -
Nuclear Medicine Communications Jun 1987p-Iodo-phentermine (IP) and two of its derivatives, N,N,-dimethyl-p-iodo-phentermine (IDMP) and N-isopropyl-p-iodo-phentermine (IIP) were synthesized and radiolabelled...
p-Iodo-phentermine (IP) and two of its derivatives, N,N,-dimethyl-p-iodo-phentermine (IDMP) and N-isopropyl-p-iodo-phentermine (IIP) were synthesized and radiolabelled with iodine by isotopic exchange. They were evaluated as potential brain imaging agents and compared to IAMP biodistribution in rats did not show any superiority to IAMP.
Topics: Animals; Brain; Iodine Radioisotopes; Male; Phentermine; Radionuclide Imaging; Rats; Rats, Inbred Strains; Tissue Distribution
PubMed: 3696629
DOI: 10.1097/00006231-198706000-00007 -
International Journal of Obesity and... Apr 1998To measure the effects of phentermine, an appetite supressant, on the release of brain dopamine (DA) and serotonin (5-HT) into striatal dialysates of freely moving rats. (Comparative Study)
Comparative Study
OBJECTIVE
To measure the effects of phentermine, an appetite supressant, on the release of brain dopamine (DA) and serotonin (5-HT) into striatal dialysates of freely moving rats.
DESIGN
Microdialysis and high performance liquid chromatography.
SUBJECTS
Unanesthetized rats.
MEASUREMENTS
Samples collected every 20 min were assayed for both neurotransmitters in a single run, using high performance liquid chromatography with electrochemical detection.
RESULTS
Baseline levels of DA and 5-HT in dialysates were 56+/-16 and 3+/-0.6 fmol/20 microl, respectively. Administration of phentermine (2 or 5 mg/kg) increased dialysate DA concentrations to 147+/-17% (P < 0.01) and 320+/-89% (P < 0.01) of baseline, respectively, without significantly affecting 5-HT concentrations. Pretreatment with tetrodotoxin (TTX, 60 min, 1 microM), which abolished the basal release of DA and 5-HT into striatal dialysates, diminished the increase in DA concentrations induced by phentermine, but did not completely block it. Phentermine (2 or 5 mg/kg, i.p.) still stimulated DA release to 27+/-13% and 85+/-15% of baseline, respectively, in the presence of TTX.
CONCLUSION
Phentermine increases brain DA but not 5-HT release in freely moving rats, and TTX reduces, but does not fully block this effect. This pattern is similar to that known to be produced by d-amphetamine.
Topics: Animals; Appetite Depressants; Cohort Studies; Corpus Striatum; Dopamine; Dose-Response Relationship, Drug; Injections, Intraperitoneal; Male; Microdialysis; Perfusion; Phentermine; Rats; Rats, Sprague-Dawley; Serotonin; Tetrodotoxin
PubMed: 9578237
DOI: 10.1038/sj.ijo.0800589 -
Postgraduate Medicine May 2021: A 34-year-old woman with no significant past medical history presented to the hospital with sudden onset of palpitations with associated dyspnea and chest discomfort....
: A 34-year-old woman with no significant past medical history presented to the hospital with sudden onset of palpitations with associated dyspnea and chest discomfort. She denied any similar previous episodes. Initial electrocardiogram (EKG) was consistent with a short R-P interval supraventricular tachycardia (SVT). Her transthoracic echocardiogram (TTE) revealed no structural abnormalities, TSH levels were normal, and urine drug screen was negative for any recreational drugs. However, the patient had been taking phentermine for weight loss.: The exact mechanism is not clear; however, we postulate that the sympathomimetic effects of phentermine likely contribute to SVT induction through enhanced AV nodal conduction or increased atrial ectopy. : The only medication she was taking at home was phentermine, and the palpitations did not recur after discontinuation of the drug during follow-up. It is important to collect a thorough medication history when patients present with AV nodal reentrant tachycardia (AVNRT) or other SVT.
Topics: Adult; Electrocardiography; Female; Humans; Phentermine; Tachycardia, Supraventricular
PubMed: 33686912
DOI: 10.1080/00325481.2021.1901476 -
Cleveland Clinic Journal of Medicine Dec 2017Weight-loss drugs are being evaluated for their role in obesity management. This article reviews the available weight-loss drugs, their efficacy and side effects, and... (Review)
Review
Weight-loss drugs are being evaluated for their role in obesity management. This article reviews the available weight-loss drugs, their efficacy and side effects, and their best clinical use.
Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Benzazepines; Bupropion; Drug Combinations; Humans; Lactones; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine
PubMed: 29244650
DOI: 10.3949/ccjm.84a.16094 -
Current Therapeutic Research, Clinical... Nov 1972
Clinical Trial Randomized Controlled Trial
Topics: Adult; Age Factors; Appetite Depressants; Body Weight; Clinical Trials as Topic; Constipation; Diet, Reducing; Female; Humans; Male; Middle Aged; Obesity; Phenethylamines; Phentermine; Placebos; Prospective Studies; Sex Factors; Sleep Initiation and Maintenance Disorders; Time Factors
PubMed: 4629111
DOI: No ID Found