Corrigendum to Article CP203292.

Cecilia Fernández Del Valle-Laisequilla, Cristian Trejo-Jasso, Juan Carlos Huerta-Cruz, Lina Marcela Barranco-Garduño, Juan Rodríguez-Silverio, Héctor Isaac Rocha-González, Juan Gerardo Reyes-García. Efficacy and safety of a fixed-dose combination of D-norpseudoephedrine, triiodothyronine, atropine, aloin, and diazepam in obese patients. Int J Clin Pharmacol Ther. 2018; 56: 531-538. doi: 10.5414/CP203292. Note from the authors: We realized only now that the affiliation of Cecilia Fernández Del Valle-Laisequilla was indicated in the title page, but due to an unintentional mistake in the final version, the affiliation was not declared in the conflict of interest section, which should read: "Cecilia Fernández Del Valle-Laisequilla is Medical Director of Productos Medix S.A. de C.V."

Combined First Month Body Weight Loss and Development of Tolerance as Predictors of 6-Month Efficacy of Mazindol in Mild and Moderate Obese Subjects.

The weight loss response to anti-obesity drugs is highly variable and poorly understood, which does not allow us to know, in advance, in which subjects the drug will be effective and in which it will not. The objective of this study was to explore the body weight reduction in kilograms in the first month (1mo-BWRkg) and the development of tolerance as predictors of 6-month efficacy for treatment with 1 mg mazindol twice a day. One hundred ninety-six obese subjects were individually or jointly analyzed. Approximately 60% of subjects developed tolerance to mazindol and achieved increasing proportional levels of 6-month efficacy according to 1mo-BWRkg intervals (<1 kg, 1 to <2 kg, 2 to <4 kg and ≥4 kg). Both moT and 1mo-BWRkg were significantly correlated with the mean percentage body weight reduction (BWR%) after 6-months of treatment. The qualitative analysis of both predictors on the progressive efficacy of mazindol was used to classify patients according to expected efficacy (inefficient, slightly effective, partially effective, or fully effective), based on the mean percentage efficacy and the number of subjects reaching a BWR% of <5%, 5 to <10%, 10 to <15% or ≥15%. In conclusion, combined 1mo-BWRkg and moT were early predictors for the progressive efficacy of 6-month mazindol anti-obesity therapy. This finding represents progress in predictive, preventive, and personalized medicine which could serve for estimating the expectations of individual efficacy with the use of the drug. and highlights the basic principle of personalized medicine, "one size does not fit all".

Metformin improves the weight reduction effect of mazindol in prediabetic obese Mexican subjects.

OBJECTIVE: Obesity is the strongest risk factor for type 2 diabetes (T2D). We aimed to explore 7% weight reduction rates of mazindol alone or combined with metformin in non-diabetic obese Mexican subjects who had additional risk factors for T2D. MATERIALS AND METHODS: In this randomized double-blind study, 137 participants received 1 mg mazindol (n = 65) alone or combined with 500 mg metformin (n = 72), twice a day, for 6 months. RESULTS: Mazindol and mazindol-metformin were similarly effective. However, when subjects were subclassified into non-diabetics and prediabetics, according to glycated hemoglobin (HbA1c) - < 5.7% and 5.7 - 6.4%, respectively - and/or fasting plasma glucose (FPG) - < 100 mg/dL and 100 - 125 mg/dL, respectively -, differences were evident. Prediabetics in the mazindol-metformin group had a higher rate of 7% weight reduction (78.4%, n = 37) compared to prediabetics treated with mazindol (48.3%, n = 29). Furthermore, mazindol-metformin treatment induced significant reductions in fasting plasma insulin, HOMA-IR, and HbA1c in prediabetics compared to mazindol. No differences were found in any parameter between non-diabetics treated with mazindol (n = 36) and mazindol-metformin (n = 35). CONCLUSION: Our results highlight the effectiveness of mazindol-metformin to achieve higher rates of 7% weight reduction and to improve the glycemic profile in prediabetic obese subjects, which could be useful to prevent or delay T2D in these subjects.

Weight Loss at First Month and Development of Tolerance as Possible Predictors of 30 mg Phentermine Efficacy at 6 Months.

The efficacy of anti-obesity drugs usually does not consider the high degree of interindividual variability in responses to the drug which could affect the decision to withdraw the drug early due to ineffectiveness or to continue therapy according to specific expectations of success. The aim of this study was to analyze body weight loss in kilograms during the first month (1 mo-BWLkg) of treatment with 30 mg phentermine and development of tolerance to phentermine, on its 6-month efficacy. One hundred sixty-six subjects with obesity were individually or jointly analyzed in the study. Subjects with 1 mo-BWLkg of <1 kg, 1-3 kg, 3-5 kg, and ≥5 kg reached 6-month mean percentage body weight reductions (BWR%) of approximately 3%, 5%, 10%, and 15%, respectively. Development of late tolerance (4-6 months) to phentermine had a lower impact than early tolerance (2-3 months). Subjects with 1 mo-BWLkg < 3 kg who developed early tolerance did not achieve relevant BWR% (≥5%) at month 6, while the rest of the subgroups achieved increasing and progressive BWR%, according to their 1 mo-BWLkg range and time of onset of tolerance. The 1 mo-BWLkg and development of tolerance to phentermine could be useful to predict the expected 6-month efficacy trends in obese patients treated with 30 mg phentermine.

Three- and six-month efficacy and safety of phentermine in a Mexican obese population.

OBJECTIVE: Mexico has the second largest prevalence of obesity among adults worldwide, a condition especially affecting the low-income population. There is a pressing need to improve therapeutic options for weight loss. Phentermine is an old and low-cost agent given as an adjuvant therapy for obesity for a 12-week period, at an initial dose of 15 mg or 30 mg. However, there are no precise guidelines on the suitability of both the starting dose and the continuation of treatment for 6 months. The aim of this study was to evaluate the 3- and 6-month efficacy and safety of phentermine in obese Mexican patients to elucidate the aforementioned. MATERIALS AND METHODS: In this prospective, multi-center, open-label study, 932 obese adults received 15 mg or 30 mg phentermine once daily for 6 months. RESULTS: 30 mg phentermine was more effective than 15 mg phentermine in improving anthropometric variables in the 3-month follow-up, but not after completing the 6-month treatment period. Nearly 40% of 3-month non-responders reached a body weight reduction of at least 5% at 6 months. Conversely, ~ 65% and 25% of 3-month responders maintained or improved, respectively, their body weight reduction with long-term phentermine. Potential tolerance as weight regain was ~ 10% from 3 to 6 months. None of the doses increased cardiovascular risk, although mild-to-moderate adverse events were more frequent with 30 mg phentermine. CONCLUSION: 30 mg phentermine was more effective than 15 mg phentermine after 3 months, but not at 6 months of treatment. An important number of subjects could benefit following the therapy from 3 to 6 months.

Pharmacokinetic evaluation of two pirfenidone formulations in patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by an abnormal activation of lung epithelium and fibroblasts, as well as an excessive accumulation of extracellular matrix. Pirfenidone was introduced as a therapeutic option for IPF and chronic hypersensitive pneumonitis (cHP), a related disease. However, high plasma concentrations, which can be achieved even at recommended doses, are frequently associated with adverse events. Hence, an extended release formulation (XP), yielding lower peak plasma concentrations, has been developed. The aim of this study was to compare the pharmacokinetic properties of XP with those of the immediate (IR) formulation in patients with IPF or cHP. Data were analyzed using two pharmacokinetic approaches, conventional non compartmental analysis and a population analysis using the nonlinear mixed effects model technique. Results observed with both approaches were consistent. Drug exposure was similar with both formulations. However, XP exhibited less concentration fluctuations and a longer mean resident time. These results suggest that XP could be a feasible option to reduce adverse events associated to pirfenidone elevated concentrations. Nevertheless, efficacy studies are required to fully document the therapeutic potential of XP.

Efficacy and safety of a fixed-dose combination of D-norpseudoephedrine, triiodothyronine, atropine, aloin, and diazepam in obese patients
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OBJECTIVE: A fixed-dose combination (FDC) of D-norpseudoephedrine, tri-iodothyronine, atropine, aloin, and diazepam is used in Mexico for the short-term treatment of obesity; however, its efficacy and safety have been scarcely studied. The aim of this study was to analyze the efficacy and safety of this FDC in Mexican adult overweight and obese patients by a prospective, uncontrolled, multicenter, phase IV open-label study. MATERIALS AND METHODS: 3,290 patients with a body mass index (BMI) ˃ 27 kg/m2 were included in the current study. Primary outcome was the absolute body weight loss, whilst secondary outcomes were the improvement of anthropometric and cardiometabolic parameters as well as the description of adverse events. RESULTS: The FDC decreased the body weight and BMI by -9.0 ± 5.6 kg and -3.4 ± 2.2 kg/m2, respectively, at 6 months. In addition, 43.3% and 14.3% of subjects achieved at least 5% or 10% weight loss at 6 months, respectively. The FDC also significantly improved waist circumference, hip circumference, body fat, visceral fat, systolic blood pressure, diastolic blood pressure, diabetes risk, and mortality risk, at 3 and 6 months. Moreover, the FDC seems to have better results in the following order: obese grade 3 ≈ obese grade 2 ˃ obese grade 1 ˃ overweight patients. Mild mouth dryness, anxiety, and headache were the main reported adverse events. CONCLUSION: Data suggest that the FDC is effective and well tolerated for the short-term therapy of overweight and obesity in Mexican patients.
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