In this study, tipranavir (TPV) biotransformation and disposition when co-administered with ritonavir (RTV) were characterized in Sprague-Dawley rats. Rats were administered a single intravenous (5 mg kg(-1)) or oral (10 mg kg(-1)) dose of [(14)C]TPV with co-administration of RTV (10 mg kg(-1)). Blood, urine, faeces and bile samples were collected at specified time-points over a period of 168 h. Absorption of TPV-related radioactivity ranged from 53.2-59.6%. Faecal excretion was on average 86.7% and 82.4% (intravenous) and 75.0% and 82.0% (oral) of dosed radioactivity in males and females, respectively. Urinary excretion was on average 4.06% and 6.73% (intravenous) and 9.71% and 8.28% (oral) of dosed radioactivity in males and females, respectively. In bile-duct-cannulated rats, 39.8% of the dose was recovered in bile. After oral administration, unchanged TPV accounted for the majority of the radioactivity in plasma (85.7-96.3%), faeces (71.8-80.1%) and urine (33.3-62.3%). The most abundant metabolite in faeces was an oxidation metabolite R-2 (5.9-7.4% of faecal radioactivity, 4.4-6.1% of dose). In urine, no single metabolite was found to be significant, and comprised <1% of dose. TPV when co-administered with RTV to rats was mainly excreted in feces via bile and the parent compound was the major component in plasma and faeces.