DA‐8159‐phase I studies to investigate the safety and pharmacokinetics in healthy male caucasian subjects

Two Phase I studies were conducted to determine the safety and pharmacokinetics of single and multiple oral doses of DA‐8159, a compound to treat male erectile dysfunction. Ascending single doses of 50, 100, 200 and 400 mg and multiple doses of 100 and 200 mg (od for 10 consecutive days) were administered. Adverse events, vital signs, 12‐lead ECG, clinical laboratory tests and physical examination were assessed. Plasma and urine samples were analysed for DA‐8159 and the metabolite DA‐8164. DA‐8159 was safe and well tolerated. DA‐8159 was rapidly absorbed and showed biphasic disposition. Systemic exposure to DA‐8 159 increased in a dose‐proportional manner over the single and multiple doses. The metabolite DA‐8164 appeared rapidly in plasma, indicating a fast metabolism of DA‐8159 to DA‐8164. The mean apparent elimination half‐life of DA‐8159 and DA‐8164 were similar, at approximately 12 h, suggesting formation‐rate limited elimination of DA‐8164. On multiple dosing, there was little or no accumulation of DA‐8159 (RA~1.3), with higher accumulation of DA‐8164 (RA~2.0). Urinary excretion of DA‐8159 was low (<12 % of the dose) and DA‐8164 was extremely low (0.2% of the dose), suggesting both DA‐8159 and DA‐8164 are subject to non‐renal elimination. Clinical Pharmacology & Therapeutics (2004) 75 , P86–P86; doi: 10.1016/j.clpt.2003.11.330