-
Molecules (Basel, Switzerland) May 2024Recently, benchtop nuclear magnetic resonance (NMR) spectrometers utilizing permanent magnets have emerged as versatile tools with applications across various fields,...
Recently, benchtop nuclear magnetic resonance (NMR) spectrometers utilizing permanent magnets have emerged as versatile tools with applications across various fields, including food and pharmaceuticals. Their efficacy is further enhanced when coupled with chemometric methods. This study presents an innovative approach to leveraging a compact benchtop NMR spectrometer coupled with chemometrics for screening honey-based food supplements adulterated with active pharmaceutical ingredients. Initially, fifty samples seized by French customs were analyzed using a 60 MHz benchtop spectrometer. The investigation unveiled the presence of tadalafil in 37 samples, sildenafil in 5 samples, and a combination of flibanserin with tadalafil in 1 sample. After conducting comprehensive qualitative and quantitative characterization of the samples, we propose a chemometric workflow to provide an efficient screening of honey samples using the NMR dataset. This pipeline, utilizing partial least squares discriminant analysis (PLS-DA) models, enables the classification of samples as either adulterated or non-adulterated, as well as the identification of the presence of tadalafil or sildenafil. Additionally, PLS regression models are employed to predict the quantitative content of these adulterants. Through blind analysis, this workflow allows for the detection and quantification of adulterants in these honey supplements.
Topics: Honey; Dietary Supplements; Magnetic Resonance Spectroscopy; Sildenafil Citrate; Workflow; Chemometrics; Tadalafil; Least-Squares Analysis; Drug Contamination; Discriminant Analysis
PubMed: 38731577
DOI: 10.3390/molecules29092086 -
Journal of Clinical Medicine Apr 2024: The management of erectile dysfunction (ED) shows several grey zones and new treatments are required to reduce the percentage of patients discontinuing treatment....
: The management of erectile dysfunction (ED) shows several grey zones and new treatments are required to reduce the percentage of patients discontinuing treatment. Here, we aim to evaluate the role of a natural mixture named Icarifil® (L-Citrulline, L-Carnitine, , , , , Taurine, Vitamin E, Zinc) in the management of patients with ED. : From September 2022 to March 2023, all patients attending 3 urological institutions due to ED were randomized to receive the following for 3 months: Icarifil® 1 sachet every 24 h (Group 1) or Icarifil® 1 sachet + tadalafil 5 mg 1 tablet every 24 h (Group 2) or tadalafil 5 mg 1 tablet daily (Group 3). All patients underwent urologic visits and dedicated questionnaires (IIEF-5, SEP-2, SEP-3) at enrollment and at the follow-up evaluation (3 months). Patient-Reported Outcomes (PROs) at the follow-up evaluation were used. The primary endpoint was the difference in the questionnaires at the follow-up visit compared to the one at enrollment among the study groups. : In the per-protocol analysis, 52 patients in Group 1, 55 in Group 2 and 57 in Group 3 were analyzed. At the follow-up evaluation, IIEF-5 scores improved in all the 3 groups between enrollment and the follow-up evaluation, but a statistically significant difference was reported between Group 2 (+7.4) and Group 1 (+4.1) or Group 3 (+5.1), ( < 0.001; < 0.001). Moreover, 47 patients (94.0%) in Group 2 showed an improvement in the SEP questionnaires, when compared with the baseline, while 29 in Group 1 (56.9%) and 42 in Group 3 (82.3%) showed a statistically significant difference ( = 0.004; = 0.003) among the groups. The PRO analysis reported better efficacy and patient satisfaction in Group 2 when compared with Group 1 or Group 3. : In conclusion, Icarifil is able to improve penile erectile function in mild-moderate ED and significantly improve the clinical efficacy of daily used tadalafil 5 mg. Icarifil could represent an interesting alternative treatment in patients experiencing adverse effects or with contraindications for chronic treatment with PDE5-is.
PubMed: 38731094
DOI: 10.3390/jcm13092564 -
Journal of the American Heart... May 2024The determinants and prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) among patients with a systemic right ventricle are largely unknown.
BACKGROUND
The determinants and prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) among patients with a systemic right ventricle are largely unknown.
METHODS AND RESULTS
Ninety-eight patients from the randomized controlled SERVE (Effect of Phosphodiesterase-5 Inhibition With Tadalafil on Systemic Right Ventricular Size and Function) trial were included. The correlation between baseline hs-cTnT concentrations and biventricular volumes and function quantified by cardiac magnetic resonance or cardiac multirow detector computed tomography was assessed by adjusted linear regression models. The prognostic value of hs-cTnT was assessed by adjusted Cox proportional hazards models, survival analysis, and concordance statistics. The primary outcome was time to the composite of clinically relevant arrhythmia, hospitalization for heart failure, or all-cause death. Median age was 39 (interquartile range, 32-48) years, and 32% were women. Median hs-cTnT concentration was 7 (interquartile range, 4-11) ng/L. Coefficients of determination for the relationship between hs-cTnT concentrations and right ventricular end-systolic volume index and right ventricular ejection fraction (RVEF) were +0.368 (=0.046) and -0.381 (=0.018), respectively. The sex- and age-adjusted hazard ratio for the primary outcome of hs-cTnT at 2 and 4 times the reference level (5 ng/L) were 2.89 (95% CI, 1.14-7.29) and 4.42 (95% CI, 1.21-16.15), respectively. The prognostic performance quantified by the concordance statistics for age- and sex-adjusted models based on hs-cTnT, right ventricular ejection fraction, and peak oxygen uptake predicted were comparable: 0.71% (95% CI, 0.61-0.82), 0.72% (95% CI, 0.59-0.84), and 0.71% (95% CI, 0.59-0.83), respectively.
CONCLUSIONS
Hs-cTnT concentration was significantly correlated with right ventricular ejection fraction and right ventricular end-systolic volume index in patients with a systemic right ventricle. The prognostic accuracy of hs-cTnT was comparable to that of right ventricular ejection fraction and peak oxygen uptake predicted.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03049540.
PubMed: 38726920
DOI: 10.1161/JAHA.123.034776 -
BMC Chemistry May 2024Alfuzosin hydrochloride and tadalafil fixed-dose combination tablets were recently formulated for the treatment of individuals with lower urinary tract symptoms caused...
Utilization of absorbance subtraction and ratio difference green spectrophotometric methods for the quantification of alfuzosin hydrochloride and tadalafil in their binary mixture.
Alfuzosin hydrochloride and tadalafil fixed-dose combination tablets were recently formulated for the treatment of individuals with lower urinary tract symptoms caused by benign prostatic hyperplasia. Herein, the first spectrophotometric methods for quantitative analysis of alfuzosin hydrochloride and tadalafil in their binary mixture were established. The spectral overlapping of alfuzosin hydrochloride and tadalafil made direct simultaneous analysis unfeasible. Therefore, two mathematical methods were used to solve these overlapping spectra: absorbance subtraction and ratio difference. The absorbance subtraction method manipulates the zero absorption spectra of the studied drugs at the isoabsorptive point (272 nm) and uses the absorbance factor of pure ALF to calculate the absorbance of the studied drugs in the mixture at the isoabsorptive point. The ratio spectra method, on the other hand, manipulates the ratio spectra of the studied drugs, which are obtained by dividing each drug's zero absorption spectra by a divisor spectrum from the second drug. The ratio amplitude difference between 251 nm and 211 nm was directly proportional to alfuzosin hydrochloride, whereas between 292 nm and 222 nm it was directly proportional to tadalafil. The methods used were verified in accordance with the recommendations of the ICH and demonstrated adequate linear regression in working ranges of 1-15 µg/mL for alfuzosin hydrochloride and 3-40 µg/mL for tadalafil. The methods were accurate, precise, and selectively employed to quantify alfuzosin hydrochloride and tadalafil in their combined tablets.
PubMed: 38725069
DOI: 10.1186/s13065-024-01201-7 -
Biomedicines Apr 2024Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition.... (Review)
Review
Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. A phase II trial we conducted provided evidence supporting the efficacy of tadalafil in prolonging pregnancy (52.4 vs. 36.8 days; = 0.03) and indicated a good safety profile for fetuses and neonates. Fetal, neonatal, and infant mortality was significantly lower in mothers receiving tadalafil treatment than that in controls (total number: 1 vs. 7, respectively; = 0.03), and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.
PubMed: 38672159
DOI: 10.3390/biomedicines12040804 -
Heliyon Apr 2024Tadalafil (TDL) has poor bioavailability due to the less aqueous solubility and bitter taste. Oral solid dosage forms, especially tablets, have a broad market worldwide....
Tadalafil (TDL) has poor bioavailability due to the less aqueous solubility and bitter taste. Oral solid dosage forms, especially tablets, have a broad market worldwide. Constraints of tablets are a long process, pollution, high processing cost, and requiring more excipient. The research was performed to optimize an eco-friendly immediate-acting pastille of TDL to put forward an alternate formulation to a tablet using advanced data mining tools. Another objective is to assess the taste masking of TDL using the Brief Access Taste Aversion BATA) model. The amount of PEG-4000, Polyox N-10, and Kyron T-314 were chosen as critical material attributes from failure mode effect analysis. Box-Behnken design (BBD) was utilized to optimize the pastilles and ascertained the significant impact of chosen variables on disintegration time and % CDR at 10 min. The control strategy and optimal region were located using an overlay plot. The pastilles were able to release the drug within 15 min due to faster disintegration. The formulated pastilles were of uniform size, shape, and mechanical strength. The bitter taste of TDL was masked and confirmed by the BATA model. The newer formulation may be helpful in the industry due to its eco-friendly, single-step, and economical process. It unlocks a new direction in the field of oral solid dosage form as an alternative to tablets.
PubMed: 38660288
DOI: 10.1016/j.heliyon.2024.e29543 -
Central European Journal of Urology 2024Ureteral stents-related symptoms (USRs) are the common complications of ureteral stenting. Tamsulosin a selective alpha-1 blocker and Tadalafil a PDE-5 inhibitor are one...
INTRODUCTION
Ureteral stents-related symptoms (USRs) are the common complications of ureteral stenting. Tamsulosin a selective alpha-1 blocker and Tadalafil a PDE-5 inhibitor are one of drugs have been used for USRs relief. In this study we aimed to evaluate the effectiveness and safety of combination therapy Tamsulosin+Tadalafil for treating USRs comparing it with the efficacy of either Tamsulosin or Tadalafil monotherapies.
MATERIAL AND METHODS
279 patients with indwelled unilateral ureteral stents were randomized to Tamsulosin 0.4 mg + Tadalafil 5 mg once a day (Group 1, n = 67), Tamsulosin 0.4 mg once a day (Group 2, n = 71), Tadalafil 5 mg once a day (Group 3, n = 69) and Placebo once a day (Group 4, n = 72). USRs severity was registered and calculated by using the Ureteral Symptoms Score Questionnaire (USSQ) at the 14 day of treatment. Side-effects and total analgesic use were recorded and compared.
RESULTS
At the endpoint in patients with unilateral ureteral stents the combination therapy Tamsulosin + Tadalafil led to statistically lower intensity of urinary symptoms comparing with Tamsulosin (15.2 ±4.3 vs 21.8±3.6, p = 0.0003) or Tadalafil (15.2 ±4.3 vs 20.6 ±2.8, p = 0.0004) monotherapy. All groups of treatment demonstrated significant relief of USRs comparing with Placebo mostly beneficial in the combined therapy group. Body pain and analgesic need in Group 1 was lower than in Groups 2, 3 or 4. Side-effects were registered rarely without statistical differences in frequency between groups.
CONCLUSIONS
Combination therapy with Tamsulosin + Tadalafil is an effective and safe option that achieves the statistically more significant relief of USRs comparing with Tadalafil or Tamsulosin monotherapies.
PubMed: 38645821
DOI: 10.5173/ceju.2023.66 -
The Journal of Pediatric Pharmacology... Apr 2024The primary outcome of this study was to describe the dosing regimen of tadalafil in neonates and infants diagnosed with pulmonary hypertension (PH) secondary to...
OBJECTIVES
The primary outcome of this study was to describe the dosing regimen of tadalafil in neonates and infants diagnosed with pulmonary hypertension (PH) secondary to bronchopulmonary dysplasia (BPD). Secondary outcomes included tolerability, efficacy, adverse events, discontinuation of therapy, and changes in echocardiography.
METHODS
This was a single-center, retrospective review of neonates and infants <1 year of age at initiation of tadalafil for PH secondary to BPD from January 2010 to November 2021. Data collected from the electronic medical record included patient demographics, tadalafil dosing, oxygen support, mechanical ventilation, concomitant PH medications, adverse events, and echocardiography information.
RESULTS
Forty-two patients-4 neonates and 38 infants-met the inclusion criteria. The postnatal and post-menstrual age (median, IQR) at diagnosis were 121 (35.5-153.5) days and 42.6 (40.6-47.6) weeks, respectively. The initial and highest tadalafil doses (median, range) were 1 (0.25-2) and 1 (0.5-2) mg/kg/day. Only 1 patient experienced pulmonary overcirculation and required tadalafil to be discontinued. Over half (57.1%) of the patients in this study discontinued tadalafil therapy owing to improvements in pulmonary artery pressures.
CONCLUSIONS
Tadalafil 1 mg/kg/day was the most commonly used dose regimen in neonates and infants. Tadalafil at this dose of 1 mg/kg/day appears well tolerated in neonates and infants with PH secondary to BPD and correlates with improvements in pulmonary artery pressures. Further studies evaluating tadalafil in comparison to other phosphodiesterase-5 inhibitors in neonates with PH secondary to BPD are warranted.
PubMed: 38596414
DOI: 10.5863/1551-6776-29.2.140 -
Sexual Medicine Apr 2024Selective androgen receptor modulators (SARMs) are small synthetic drug molecules that are still not approved as medicine in Europe or the United States but are sold on...
BACKGROUND
Selective androgen receptor modulators (SARMs) are small synthetic drug molecules that are still not approved as medicine in Europe or the United States but are sold on illegal websites to improve sport performance, particularly bodybuilding.
AIM
To address the quality issues of illegal SARM products and their increasing diffusion in Italy with their potential health risks for consumers.
METHODS
Web-based tools were used to investigate retail websites, trending searches, and information exchange via social media. Thirteen SARM products, purchased on retail websites accessible from Italy, were subject to visual inspection and chemical analysis by mass spectrometry and quantitative nuclear magnetic resonance.
OUTCOMES
The primary outcome was demonstration of additional health risks due to the illicit presence of other active ingredients, contamination, and misdosage in SARM products sold on the internet. The secondary outcome was to show the increasing trend of interest in Italy for these products.
RESULTS
Most websites reported misleading information; specifically, the statement "for research only" was reported notwithstanding indications on dosage and training phases. The trending search showed that interest toward SARMs increased in Italy in the last years. The use of these products is clearly encouraged by the emerging phenomenon of "broscience" as revealed in socials. Visual inspection evidenced nonconform labeling. Qualitative analysis confirmed the presence of the stated SARM in about 70% of samples. In 23% of samples, the expected SARM was not detected but a different one instead, and in 1 sample, no SARMs were detected. Other undeclared pharmaceutical substances (tamoxifen, clomifene, testosterone, epimethandienone, tadalafil) were measured in 30% of samples. The copresence of >1 active substance was observed in >60% of samples. Quantitative nuclear magnetic resonance data showed nonuniform content ranging from 30% to 90% of the label claim.
CLINICAL IMPLICATIONS
The use of SARMs, in the presence of unexpected life-threatening reactions in persons using the products to increase sport performance, should be assessed.
STRENGTHS AND LIMITATIONS
This investigation involved an integrated approach to study SARM products and related sociologic aspects. The main shortcomings are the limited number of samples and retail websites in the clear web investigated.
CONCLUSION
SARMs sold online as food supplement-like products represent a health hazard due to the presence of unapproved and undeclared active substances. The presence of contaminants clearly indicates the absence of good manufacturing practices in the production, which increases the health risks.
PubMed: 38560649
DOI: 10.1093/sexmed/qfae018