TABLE 3.
Pharmacokinetic parameters of pitavastatin and pitavastatin lactone.
| 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) | ||
| Pitavastatin | ||||||||
| AUC0-last (pg/mL.hr) | 429 (375–491) | 1,956 (1,656–2,312) | 4.56 (3.71–5.61)* | 446 (375–530) | 1.04 (0.82–1.31) | 715 (578–885) | 1.67 (1.33–2.09)*,¶ | |
| AUC0-inf (pg/mL.hr) | 468 (405–540) | 1,980 (1,677–2,339) | 4.24 (3.42–5.24)* | 494 (417–585) | 1.06 (0.83–1.34) | 774 (624–959) | 1.66 (1.32–2.08)*,¶ | |
| Cmax (pg/mL) | 159 (132–191) | 857 (729–1,008) | 5.40 (4.25–6.86)* | 154 (123–192) | 0.97 (0.73–1.28) | 242 (193–303) | 1.53 (1.16–2.00)*,¶ | |
| Tmax (hr)a | 0.7 (0.7–0.7) | 0.7 (0.7–0.7) | – | 0.7 (0.7–0.7) | – | 0.7 (0.7–0.7) | – | |
| T1/2 (hr)a | 12.2 (10.7–14.1) | 6.5 (4.8–9.6)* | – | 12.6 (11.4–15.9) | – | 15.0 (11.3–17.6) | – | |
| CL/F (mL/min/kg0.75) | 19 (17–21) | 4 (4–5) | 0.22 (0.19–0.26)* | 17 (15–20) | 0.92 (0.74–1.13) | 10 (8–12) | 0.53 (0.43–0.65)*,¶ | |
| Pitavastatin lactone | ||||||||
| AUC0-last (pg/mL.hr) | 524 (440–623) | 649 (556–759) | 1.24 (0.99–1.56) | 604 (494–739) | 1.15 (0.89–1.50) | 950 (767–1,177) | 1.81 (1.41–2.34)*,¶ | |
| AUC0-inf (pg/mL.hr) | 574 (475–693) | 690 (589–809) | 1.20 (0.95–1.53) | 676 (558–819) | 1.18 (0.90–1.54) | 1,071 (861–1,332) | 1.87 (1.44–2.42)*,¶ | |
| Cmax (pg/mL) | 59 (51–68) | 76 (67–86) | 1.29 (1.08–1.55)* | 48 (58–69) | 0.98 (0.78–1.22) | 80 (66–97) | 1.35 (1.09–1.68)*,¶ | |
| Tmax (hr)a | 1.5 (1.0–1.8) | 1.5 (1.0–2.0) | – | 1.5 (1.5–1.5) | – | 1.5 (1.5–2.0) | – | |
| T1/2 (hr)a | 13.1 (8.6–17.6) | 12.8 (8.9–18.1) | – | 13.7 (11.6–17.9) | – | 15.3 (12.2–19.0) | – | |
| Pitavastatin lactone/ P itavastatin ratio | ||||||||
| AUC0-last | 1.22 (1.08–1.38) | 0.33 (0.30–0.37) | 0.40 (0.34–0.47)* | 1.35 (1.22–1.51) | 1.13 (0.89–1.43) | 1.33 (1.15–1.54) | 1.13 (0.90–1.41) | |
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-inf: area under the concentration-time curve of time zero to infinity; AUC0-last: area under the concentration-time curve of time zero to the last time point; CL/F: oral clearance; CI: confidence interval; Cmax: maximum plasma concentration; GM: geometric mean; GMR: geometric mean ratio; Tmax: time to maximum plasma concentration; T1/2: half-life.