Purpose To conduct a population pharmacokinetic (PK) analysis assessing the effects of renal function and other covariates on rosuvastatin (RO) pharmacokinetics. Methods: A total of 10,078 RO plasma values collected from 16 clinical trials after single/multiple oral dosing of 5 to 80 mg RO to 945 volunteers, renal-impaired subjects, or dyslipidemic subjects (DS) were used. A structural PK model was built using data from 10 phase I studies. Demographic covariates, creatinine clearance (CLCR), and RO dose were evaluated. Results: Structural PK model was a two-compartment model with linear elimination and simultaneous first- and zero-order absorption. Final model parameters (typical values) are: CL/F (257 L/hr), VC/F (899 L), V2/F (1380 L), Q2/F (67.9 L/hr), Ka (1.14 hr−1), D2 (4.48 hr), and F2(0.857). Age, smoking status, body weight, body surface area, and lean body mass had no effect on any PK parameters. CL/F was not significantly changed in subjects with mild/moderate renal impairment. CL/F was decreased in Japanese living in Japan (56% of Caucasians) and in DS (29% of volunteers). VC/F increased with increasing IBW slightly or in DS (153% of volunteers). Compared to Caucasians, Japanese exhibited lower V2/F (72%) and Ka (42%) and Black had lower Ka (5%) and D2 (69%). Females had a lower D2 (77% of males). Conclusions: Mild or moderate renal impairment did not alter RO PK. Ethnicity and subject status are 2 factors influencing systemic exposure to RO. Clinical Pharmacology & Therapeutics (2004) 75, P56–P56; doi: 10.1016/j.clpt.2003.11.214
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Tsang‐Bin Tzeng (2004) studied this question.