Investigation of Interactive Activity of Electro-Acupuncture on Pharmacokinetics of Sildenafil and Their Synergistic Effect on Penile Blood Flow in Rats.

Erectile dysfunction (ED) is a disorder found in males throughout the world, which negatively affects relationships with partners with advancing age. Hence, in this study, we tested a combined novel treatment of electro-acupuncture (EA) and sildenafil citrate against ED. In addition to EA therapy, the sildenafil citrate, a phosphodiesterase 5 inhibitor, is a widely recognized drug that has achieved considerable success in the treatment of ED. However, the combined effect of both the EA and sildenafil has not yet been investigated. Hence, we aimed to examine the effect of EA on the pharmacokinetics and pharmacodynamics of sildenafil in rat plasma. The pharmacokinetic parameters were determined using ultra performance liquid chromatography (UPLC) after EA and sildenafil administration (10 mg/Kg). Following this, the pharmacodynamics was studied via blood flow pattern using developing Doppler images of the lower body and penis. The pharmacokinetic studies demonstrated that sildenafil significantly increases by administration of low-frequency EA. Further, the pharmacodynamic studies using Doppler imaging revealed an elevated blood flow in rat penis compared with lower body during combined treatment of sildenafil and low-frequency EA. These data indicate a synergistic therapeutic effect of EA and sildenafil for the treatment of ED.

Comparative Randomized Crossover Clinical Study for the Evaluation of Erectile Dysfunction Medications Via Novel Pentagon System.

INTRODUCTION: Due to the chaos in the legislation in the Middle East, male enhancement nutraceuticals may be sold without any registration or evaluation. These products need to be evaluated with respect to safety and efficacy. Furthermore, cultural and social considerations in the Middle East prevent the use of international evaluations schemes for erectile dysfunction. AIM: Evaluating the safety and efficacy parameters of generic and nutraceutical products for erectile dysfunction in the Middle East through a custom-designed, representable and simple system tailored to the regional culture. METHODS: 74 healthy male volunteers were enrolled into a comparative, simple randomized, single dose, double blind, and crossover clinical study incorporated with a tailored-designed questionnaire. Safety assessment included laboratory analysis for liver functions and measuring blood pressure. MAIN OUTCOME MEASURES: Subjective data regarding safety and efficacy were assessed from the validated questionnaire. Blood pressure was measured. Blood samples were collected to assess the drug/adulterants concentration and liver and kidney functions. RESULTS: All tested nutraceuticals showed undeclared Sildenafil citrate in patients. Questionnaire results showed high inter-patient variability with respect to efficacy and comparable safety profile compared to Viagra®. CONCLUSION: The validated tailored-designed questionnaire effectively assessed the efficacy and safety of male enhancement products. The male enhancement nutraceuticals, sold in Egypt, claimed to be 100% natural are adulterated and of questionable safety profile.

A Case Report of Fatal Desmethyl Carbodenafil Toxicity.

We present the case report of a 34-year-old Hispanic male who was found unresponsive in the carport of his residence. Surveillance video footage from a security camera showed that he collapsed as he was walking to his vehicle. The decedent had no medical history and no history of illicit drug use. Initial toxicology testing revealed no alcohol or illicit drugs. Autopsy findings indicated a need for additional toxicological analysis due to a lack of trauma and the paucity of pathophysiologically significant natural disease. Liquid chromatography time-of-flight mass spectrometry of postmortem blood revealed the presence of two large peaks corresponding to desmethyl carbodenafil, an unapproved sildenafil analogue and its hydroxy metabolite. Species that are probable desmethyl and hydroxydesmethyl metabolites of desmethyl carbodenafil were also found. The mass and retention time of the parent compound in the decedent's sample were matched to those of a commercial standard. Based on this preliminary match, a method was developed and validated to quantify desmethyl carbodenafil in human blood. This is the first known case of fatal intoxication by desmethyl carbodenafil, a phosphodiesterase-5 inhibitor that is not approved for use in the United States. Over the past several years, retailers have issued voluntary recalls for dietary supplements marketed as sexual performance enhancers on the basis that these supplements may contain undeclared desmethyl carbodenafil.

Dual ß-cyclodextrin functionalized Au@SiC nanohybrids for the electrochemical determination of tadalafil in the presence of acetonitrile.

This finding described the electrochemical detection of tadalafil based on CM-ß-cyclodextrin and SH-ß-cyclodextrin functionalized Au@SiC nanohybrids film. The tadalafil electrochemical signal could be dramatically amplified by introducing 40% of acetonitrile in buffer medium and further enhanced by the host-guest molecular recognition capacity of ß-cyclodextrin. Uniform and monodispersed ~5.0 nm Au NPs were anchored on the SiC-NH2 surface via a chemical reduction process by using polyethylene glycol and sodium citrate as dispersant and stabilizing agent. CM-ß-CD was covalently bound on Au@SiC by combining the amine group of SiC-NH2 with the carboxyl group of CM-ß-CD with the aid of EDC/NHS coupling agent. SH-ß-CD could tightly attach to the surface of Au@SiC by the strong coordinating capability between Au and thiol. Differential pulse voltammetry was successfully used to quantify tadalafil within the concentration range of 0.01-100 µM under optimal conditions with a detection limit (S/N = 3) of 2.5 nM. In addition, the ß-CD-Au@SiC nanohybrid electrochemical sensor showed high selectivity to two other erectile dysfunction drugs sildenafil and vardenafil. The proposed electrochemical sensing platform was successfully used to determine tadalafil in raw materials, herbal sexual health products, and spiked human serum samples.