Steady state population pharmacokinetics of a non-commercial immediate release metformin (hydrochloride) drug product were characterized in 28 severely obese children with insulin resistance. The concentration-time profiles with double peaks were well described by a one-compartment model with two absorption sites. Mean population apparent clearance (CL/F) was 68.1 L/hr and mean apparent volume of distribution (V/F) was 28.8 L. Body weight was a covariate of CL/F and V/F. Estimated glomerular filtration rate was a significant covariate of CL/F (p<0.001). SLC22A1genotype did not significantly affect metformin pharmacokinetics. The response to 6 months of metformin treatment (HbA1c, HOMA IR, fasting insulin, and glucose changes) was not different between SLC22A1 wild type subjects and carriers of presumably low activity SLC22A1 alleles. However, SLC22A1 variant carriers had smaller reductions in percentage of total trunk fat after metformin therapy, although the percentage reduction in trunk fat was small. The median % change in trunk fat was −2.20 % (−9.00 % – 0.900 %) and −1.20 % (−2.40 % – 7.30 %) for the SLC22A1 wild-type subjects and variant carriers, respectively. Future study is needed to evaluate the effects of SLC22A1 polymorphisms on metformin-mediated weight reduction in obese children.
The present paper reports the chemical analysis of the methanolic extracts of fermented and non-fermented Cyclopia genistoides herbs and an investigation of the xanthine oxidase inhibitory activity of the isolated constituents. Chemical analysis of the leaves and stems of C. genistoides yielded the isolation and identification of two benzophenone glucosides, iriflophenone 2-O-β-glucopyranoside (1) and iriflophenone 3-C-β-glucopyranoside (2), two pterocarpans, (6aR,11aR)-(-)-2-methoxymaackiain (5) and (6aR,11aR)-(-)-maackiain (6), along with the flavanones liquiritigenin (9) and hesperetin (10), the flavone diosmetin (11), the isoflavones afrormosin (7) and formononetin (8), piceol (3), and 4-hydroxybenzaldehid (4). Among the eleven compounds, nine are reported for the first time from this species, and six from the genus Cyclopia. These compounds, together with previously isolated secondary metabolites of this species, were tested for xanthine oxidase inhibitory activity. The 5,7-dihydroxyflavones luteolin and diosmetin significantly inhibited the enzyme in vitro, while hesperetin (10) and 5,7,3',5'-tetrahydroxyflavone exerted weak activity.
Background: Slimming products represent a dynamically growing group of food supplements worldwide. The efficacy of safely usable natural ingredients is usually below consumers’ expectations. Certain manufacturers add unauthorized or prohibited ingredients to weight loss supplements in order to increase their efficacy. Hence, many of these products are adulterated and may pose a risk to the consumers’ health.Aims: The aim of our work was to give an overview on natural ingredients used in slimming products, to summarize the frequently used synthetic adulterants and also to assess the trends of adulterated and illegal food supplements in the European Union based on the warnings of the Rapid Alert System for Food and Feed (RASFF) in the time period of 1988–2019.Methods: Reports between 1988–2019 were extracted from the RASFF portal on January 1, 2020. Each entry was individually reviewed.Results: 2,559 records of food supplements with quality problems were identified in the RASFF, several of which [319 (12,5%)] were marketed to facilitate weight loss. 202 (63,3%) contained unapproved, synthetic drug ingredients. The major adulterant (113 of 319, 35.4%) was DNP (2,4-dinitrophenol), whereas sibutramine was the second most frequent adulterant agent (69 products, 21,6%) between 1988 and 2019.Conclusion: The number of approved medicines for the indication of weight loss is relatively low and their efficacy (and also that of the natural ingredients) is limited. Therefore, a significant number of weight loss supplements is adulterated to satisfy patients’ expectations. Hence, these products may cause serious adverse effects in sensitive patients.
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