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.

A Non-Fatal Self-Poisoning Attempt with Sildenafil.

The phosphodiesterase type 5 inhibitor, sildenafil, is not generally known for its use as a self-poisoning drug. However, intoxication cases with lethal outcome have been described. The case presented here is of a 56-year-old man who claimed to have undertaken an unsuccessful suicide attempt by mono-ingestion of 65 tablets of 100 mg sildenafil. He arrived at the emergency department 24 h after intake with severe vomiting and symptoms of blurred vision. Clinical examination revealed no priapism. Of note was a sinus tachycardia of 100 bpm without signs of hypotension. To quantify the sildenafil concentration in serum, an high-performance liquid chromatography photo-diode array method was developed and validated according to European Medicines Agency guidelines. The intoxicated patient had a serum concentration of 22.2 µg/mL sildenafil, at the time of presentation, which is far above the therapeutic peak concentration. The serum concentration further declined to 9.2 and 2.3 µg/mL, respectively, 5 and 14 h later, revealing a biological half-life of 4.2 h. To the best of our knowledge, this patient took the highest sildenafil dose, which resulted in the highest serum concentration, ever reported. In this subject, sildenafil showed good tolerability because few symptoms occurred and only moderate supportive therapy was needed for full recovery without sequelae.

Histological alterations in the testicular tissue induced by sildenafil overdoses.

Twenty adult male rabbits (Oryctolagus cuniculus) received sildenafil (0, 1, 3, 6, 9 mg/kg/day) for 4 weeks to investigate the testicular histological alterations induced by overdoses of this drug. Exposure to overdoses of sildenafil had provoked tubular and interstitial histological alterations. Abnormality in the germinal epithelium of the seminiferous tubules included spermatocytes karyopyknosis, spermatocytes degeneration, desquamation, spermatid giant cells and arrest of spermatogenesis. Additionally, increased Leydig cells cellularity, tubular degeneration, thickening of the interstitium were also observed. The encountered histological findings indicate that chronic exposure to sildenafil overdoses produces significant morphological and histological alterations in the testes which finally might lead to complete arrest of spermatogenesis.