TABLE 4.
Pharmacokinetic parameters of atorvastatin, 4-hydroxy atorvastatin, rosuvastatin, and rosuvastatin with ABCG2 gene wild-type (rs2231142).
| Drugs | Healthy young adults | Healthy elderly | Elderly patients with chronic kidney disease | ||||
|---|---|---|---|---|---|---|---|
| Microdose | Microdose + Rifampicin | Microdose | Microdose | ||||
| GM (95%CI) | GM (95%CI) | GMR (95%CI) | GM (95%CI) | GMR (95%CI) | GM (95%CI) | GMR (95%CI) | |
| Atorvastatin | |||||||
| AUC0-last (pg/mL.hr) | 131 (102–168) | 767 (609–965) | 5.84 (4.21–8.10)* | 281 (228–347) | 2.14 (1.52–3.02)* | 545 (411–725) | 4.15 (2.98–5.79)*,¶ |
| Cmax (pg/mL) | 16 (12–21) | 258 (196–339) | 16.37 (11.25–23.81)* | 35 (27–45) | 2.22 (1.49–3.31)* | 66 (47–92) | 4.18 (2.85–6.14)*,¶ |
| Tmax (hr)a | 0.3 (0.3–0.3) | 0.7 (0.7–1.0)* | – | 0.3 (0.3–0.3) | – | 0.3 (0.3–0.3) | – |
| CL/F (mL/min/kg0.75) | 617 (479–793) | 106 (88–126) | 0.17 (0.13–0.23)* | 274 (219–342) | 0.44 (0.31–0.63)* | 131 (100–173) | 0.21 (0.15–0.30)*,¶ |
| 4-Hydroxy atorvastatin | |||||||
| AUC0-last (pg/mL.hr) | 94 (74–120) | 729 (590–901) | 7.75 (5.67–10.58)* | 146 (113–187) | 1.55 (1.12–2.14)* | 243 (194–304) | 2.58 (1.88–3.53)*,¶ |
| Cmax (pg/mL) | 7 (6–8) | 109 (89–134) | 16.08 (12.40–20.86)* | 9 (7–11) | 1.27 (0.94–1.72) | 12 (9–17) | 1.84 (1.37–2.47)*,¶ |
| Tmax (hr)a | 5.0 (4.0–8.0) | 2.0 (1.0–2.5)* | – | 8.0 (6.0–10.0) | – | 6.0 (4.0–10.0) | – |
| 4-Hydroxy atorvastatin/atorvastatin ratio | |||||||
| AUC0-last | 0.72 (0.57–0.90) | 0.95 (0.84–1.07) | 1.20 (0.96–1.50) | 0.52 (0.42–0.64) | 0.78 (0.64–0.96)* | 0.45 (0.37–0.53) | 0.72 (0.59–0.87)* |
| Rosuvastatin | |||||||
| AUC0-last (pg/mL.hr) | 195 (133–288) | 851 (690–1,050) | 4.35 (2.84–6.67)* | 290 (228–369) | 1.48 (0.95–2.32)* | 372 (279–495) | 1.90 (1.23–2.93)* |
| Cmax (pg/mL) | 32 (23–45) | 232 (177–305) | 7.21 (4.78–10.89)* | 37 (31–45) | 1.15 (0.78–1.69) | 53 (40–70) | 1.63 (1.12–2.37)* |
| Tmax (hr)a | 3.5 (1.8–4.0) | 1.0 (1.0–1.5)* | – | 4.0 (3.0–4.0) | – | 2.0 (1.0–3.0) | – |
| CL/F (mL/min/kg0.75) | 207 (144–297) | 48 (39–57) | 0.23 (0.15–0.34)* | 133 (106–167) | 0.64 (0.42–0.98)* | 96 (73–127) | 0.47 (0.31–0.70)* |
| CLR (mL/min) | 223 (192–259) | 147 (131–164) | 0.66 (0.55–0.79)* | 157 (126–195) | 0.70 (0.51–0.97)* | 42 (30–60) | 0.19 (0.14–0.26)*,¶ |
| Rosuvastatin with ABCG2 gene wild-type (rs2231142) | |||||||
| AUC0-last (pg/mL.hr) | 136 (91–203) | 700 (570–860) | 5.15 (3.36–7.89)* | 274 (180–419) | 2.02 (1.16–3.51)* | 285 (193–419) | 2.09 (1.26–3.49)* |
| Cmax (pg/mL) | 25 (17–37) | 203 (143–290) | 8.04 (4.87–13.28)* | 39 (33–47) | 1.56 (0.97–2.50) | 40 (30–52) | 1.57 (1.01–2.44)* |
aData are presented in the median (interquartile range).
*p-value <0.05, healthy young adult as a reference group.
¶p-value <0.05, healthy elderly as a reference group.
AUC0-last: area under the concentration-time curve of time zero to the last time point; CI: confidence interval; CL/F: oral clearance; CLR: renal clearance; Cmax: maximum plasma concentration; GM: geometric mean; GMR: geometric mean ratio; Tmax: time to maximum plasma concentration; T1/2: half-life.