Encysive Pharmaceuticals announced results from a 24-subject drug interaction study of Thelin (sitaxsentan) and Viagra (sildenafil) which demonstrated a minor pharmacokinetic drug-drug interaction.
In the study, a group of 24 normal healthy volunteers participated in two treatment periods. In one, they received Thelin (100 mg) for seven days and a single dose of Viagra (100 mg) on the seventh day. In the other treatment period they received seven days of placebo and 100 mg of Viagra on the seventh day. Subjects were randomly assigned to which treatment they received first. Blood was drawn to determine plasma levels of sitaxsentan, sildenafil and sildenafil's active metabolite n-desmethyl sildenafil, an official release said.
Results showed that sildenafil administration did not appear to alter sitaxsentan levels. In the presence of sitaxsentan, the Cmax (maximum concentration) of sildenafil increased by 18 per cent and the AUC (area under the plasma concentration/time curve) increased by 28 per cent. No effects on levels of the n-desmethyl sildenafil were observed.
"Based on these data, Viagra doesn't appear to impact Thelin pharmacokinetics. Thelin showed a minor effect on overall Viagra pharmacokinetics, presumably based on the expected, weak, cytochrome P450 3A4 inhibition seen in cultured hepatocytes," said Terrance C Coyne, vice president of Clinical Development and Chief Medical Officer of Encysive Pharmaceuticals. "In consideration of discussions of other drug interactions in the Viagra package insert, our findings suggest that administration of a combination of Thelin and Viagra should not require adjustment of either the Viagra or Thelin dosages," added Dr. Coyne.
"Neither Thelin nor Viagra are approved for use in pulmonary arterial hypertension (PAH). However, both are under active investigation for PAH and we are aware that interest is high, As such, we felt it was important to evaluate the potential for a drug interaction and to report the results promptly," stated Bruce D Given, president and CEO of Encysive Pharmaceuticals.
Thelin is a small molecule that blocks the action of endothelin, a potent mediator of blood vessel constriction and growth of smooth muscle in vascular walls. Endothelin receptor antagonists may prove to be effective in the treatment of a variety of diseases where the regulation of vascular constriction is important. Thelin is 6,500 fold selective in the targeting of the endothelin receptor.
Pulmonary arterial hypertension (PAH) is a condition that involves high blood pressure and structural changes in the walls of the pulmonary arteries, which are the blood vessels that connect the right side of the heart to the lungs. PAH causes shortness of breath, limits activity, and is eventually fatal unless treated successfully with heart and lung transplant. Primary and secondary PAH are estimated to afflict approximately 80,000 to 100,000 people worldwide, many of whom are children and young women.
Encysive Pharmaceuticals Inc, a biopharmaceutical company focused on the discovery, development and commercialization of novel drugs, is expert in small molecule drug development and vascular biology.