PT  - JOURNAL ARTICLE
AU  - Cheng, H
AU  - Schwartz, M S
AU  - Vickers, S
AU  - Gilbert, J D
AU  - Amin, R D
AU  - Depuy, B
AU  - Liu, L
AU  - Rogers, J D
AU  - Pond, S M
AU  - Duncan, C A
TI  - Metabolic disposition of simvastatin in patients with T-tube drainage.
DP  - 1994 Jan 01
TA  - Drug Metabolism and Disposition
PG  - 139--142
VI  - 22
IP  - 1
4099  - http://dmd.aspetjournals.org/content/22/1/139.short
4100  - http://dmd.aspetjournals.org/content/22/1/139.full
SO  - Drug Metab Dispos1994 Jan 01; 22
AB  - A study to investigate the disposition and biliary excretion of simvastatin (SV) was conducted in four cholecystectomy patients with T-tube drainage. Each patient received a single oral dose of 100 mg of [14C]SV (20 microCi). Of the 14C-labeled dose, approximately 35% was excreted in urine, 25% in bile, and 20% in feces. Thus, at least 60% of the oral dose was absorbed from the gastrointestinal tract. Of the AUC for radioactivity in plasma, 13% was contributed by the HMG-CoA reductase inhibitors. In addition, only 2% of the 14C-dose was eliminated in urine as HMG-CoA reductase inhibitors. Thus, most of the SV-related compounds in plasma and urine have little or no HMG-CoA reductase inhibitory activity. The same is probably true for these compounds in bile. Two major active metabolites were present in the bile. Based on HPLC and MS/MS data, they were identified as 6' beta-COOH-SVA and 6'-OH-SVA. In general, the majority of the radioactivity in the bile and urine was excreted within 24 hr postdose. Of the radioactivity excreted in the 0- to 24-hr bile, on average, approximately 30% was contributed by 6' beta-COOH-SVA and 6'-OH-SVA. These two metabolites accounted for the majority of HMG-CoA reductase inhibitory activity in the bile. Little or SV or no SVA was present in the bile.