Metabolism, excretion, and pharmacokinetics of rosuvastatin in healthy adult male volunteers

• Published in: Clinical therapeutics 2003-11, Vol.25 (11), p.2822-2835
• Main Authors: Martin, Paul D., Warwick, Mike J., Dane, Aaron L., Hill, Steve J., Giles, Petrina B., Phillips, Paul J., Lenz, Eva
• Format: Article
• Language: English
• Subjects: Adult; Area Under Curve; Biological and medical sciences; Biological Availability; Carbon Isotopes; Chromatography, High Pressure Liquid; excretion; Fluorobenzenes - blood; Fluorobenzenes - pharmacokinetics; Fluorobenzenes - urine; General and cellular metabolism. Vitamins; Half-Life; HMG-CoA-reductase inhibitor; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - blood; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - urine; Male; Medical sciences; Metabolic Clearance Rate; metabolism; Middle Aged; pharmacokinetics; Pharmacology. Drug treatments; Pyrimidines - blood; Pyrimidines - pharmacokinetics; Pyrimidines - urine; rosuvastatin; Rosuvastatin Calcium; Sulfonamides - blood; Sulfonamides - pharmacokinetics; Sulfonamides - urine
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(03)80336-3

Background: Rosuvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitor, or statin, that has been developed for the treatment of dyslipidemia. Objective: This study assessed the metabolism, excretion, and pharmacokinetics of a single oral dose of radiolabeled rosuvastatin ([ 14C]-rosuvastatin) in healthy volunteers. Methods: This was a nonrandomized, open-label, single-day trial. Healthy adult male volunteers were given a single oral dose of [ 14C]-rosuvastatin 20 mg (20 mL [ 14C]-rosuvastatin solution, nominally containing 50 μCi radioactivity). Blood, urine, and fecal samples were collected up to 10 days after dosing. Tolerability assessments were made up to 10 days after dosing (trial completion) and at a follow-up visit within 14 days of trial completion. Results: Six white male volunteers aged 36 to 52 years (mean, 43.7 years) participated in the trial. The geometric mean peak plasma concentration (C max) of rosuvastatin was 6.06 ng/mL and was reached at a median of 5 hours after dosing. At C max, rosuvastatin accounted for ∼50% of the circulating radioactive material. Approximately 90% of the rosuvastatin dose was recovered in feces, with the remainder recovered in urine. The majority of the dose (∼70%) was recovered within 72 hours after dosing; excretion was complete by 10 days after dosing. Metabolite profiles in feces indicated that rosuvastatin was excreted largely unchanged (76.8% of the dose). Two metabolites—rosuvastatin-5S-lactone and N-desmethyl rosuvastatin—were present in excreta. [ 14C]-rosuvastatin was well tolerated; 2 volunteers reported 4 mild adverse events that resolved without treatment. Conclusions: The majority of the rosuvastatin dose was excreted unchanged. Given the absolute bioavailability (20%) and estimated absorption (∼50%) of rosuvastatin, this finding suggests that metabolism is a minor route of clearance for this agent.