TABLE 2

Pharmacokinetic variables of repaglinide after a single oral dose of 0.25 mg of repaglinide in nine healthy volunteers, after pretreatment with 600 mg of gemfibrozil twice daily, when repaglinide was administered 1, 24, 48, or 96 h after the last gemfibrozil dose

Values are mean ± S.D.

VariableControlTime from the Last Gemfibrozil Dose
1 h24 h48 h96 h
Repaglinide
    Cmax (ng/ml)3.0 ± 1.17.9 ± 1.9***5.6 ± 1.5***,††3.7 ± 1.4†††,‡‡‡3.2 ± 1.1†††,‡‡‡
    -Fold (range)2.7 (1.5–3.7)1.9 (1.3–3.3)1.2 (0.7–2.1)1.1 (0.7–1.6)
    t1/2 (h)1.6 ± 0.23.2 ± 0.6***1.8 ± 0.2*,†††1.7 ± 0.3†††1.7 ± 0.4†††
    -Fold (range)2.0 (1.6–3.0)1.1 (1.0–1.3)1.1 (0.9–1.3)1.1 (0.9–1.3)
    AUC0–9 h (ng × h/ml)4.2 ± 2.027.6 ± 5.3***11.9 ± 4.0***,†††5.9 ± 2.4***,†††,‡‡‡4.1 ± 1.5†††,‡‡‡,¶¶
    -Fold (range)6.6 (3.5–10.6)2.8 (2.2–3.7)1.4 (1.2–1.8)1.0 (0.8–1.3)
    AUC0–∞ (ng × h/ml)4.3 ± 2.032.5 ± 5.7***12.3 ± 4.3***,†††6.1 ± 2.5***,†††,‡‡‡4.2 ± 1.5†††,‡‡‡,¶¶
    -Fold (range)7.6 (4.2–12.0)2.9 (2.2–3.8)1.4 (1.2–1.8)1.0 (0.8–1.4)
M1
    Cmax (U/ml)3.8 ± 1.16.6 ± 2.0**4.6 ± 1.64.0 ± 1.5†††4.0 ± 0.9†††
    -Fold (range)1.7 (1.2–2.8)1.2 (0.8–2.3)1.1 (0.6–1.6)1.0 (0.7–1.6)
    t1/2 (h)0.9 ± 0.23.0 ± 0.7***1.5 ± 0.2***,†††1.1 ± 0.3*,†††,0.8 ± 0.2†††,‡‡‡,
    -Fold (range)3.5 (2.2–4.9)1.7 (1.2–3.0)1.2 (0.9–1.7)0.9 (0.7–1.4)
    AUC0–9 h (U × h/ml)6.2 ± 1.727.9 ± 9.2***10.6 ± 3.5***,†††7.3 ± 2.5†††,‡‡‡6.3 ± 1.7†††,‡‡‡
    -Fold (range)4.5 (2.7–6.3)1.7 (1.2–2.2)1.2 (0.9–1.7)1.0 (0.8–1.5)
    AUC0-∞ (U × h/ml)6.8 ± 1.433.0 ± 10.6***12.0 ± 3.4***,†††8.2 ± 2.3*,†††,‡‡‡6.7 ± 2.0†††,,
    -Fold (range)4.9 (3.3–6.8)1.8 (1.3–2.2)1.3 (1.0–1.6)1.0 (0.8–1.6)
    M1/repaglinide AUC0–9 h ratio (U/ng)1.7 ± 0.51.0 ± 0.3**0.9 ± 0.3***1.3 ± 0.4**,‡‡‡1.7 ± 0.6†††,‡‡‡,¶¶
    -Fold (range)0.6 (0.3–1.4)0.6 (0.4–0.8)0.8 (0.5–1.1)1.0 (0.6–1.5)
M2
    Cmax (U/ml)10.5 ± 4.29.8 ± 4.810.6 ± 4.810.3 ± 4.312.6 ± 7.1
    -Fold (range)0.9 (0.5–1.3)1.0 (0.7–1.8)1.0 (0.6–1.3)1.2 (0.8–1.4)
    t1/2 (h)0.9 ± 0.33.3 ± 1.1***1.7 ± 0.5***,††1.2 ± 0.4*,†††,0.9 ± 0.3†††,
    -Fold (range)3.7 (2.2–6.1)1.9 (1.2–2.6)1.3 (0.9–2.5)1.0 (0.5–1.9)
    AUC0–9 h (U × h/ml)19.8 ± 12.434.1 ± 14.9***27.9 ± 13.0*22.0 ± 11.6††,22.4 ± 14.3**,†††
    -Fold (range)1.7 (1.1–2.7)1.4 (0.9–2.3)1.1 (0.8–1.4)1.1 (0.9–1.6)
    AUC0–∞ (U × h/ml)20.6 ± 12.641.6 ± 16.4***30.3 ± 13.6*,23.2 ± 11.8†††,23.4 ± 14.4*,†††,
    -Fold (range)2.0 (1.6–3.0)1.5 (1.0–2.2)1.1 (0.8–1.5)1.1 (0.9–1.6)
    M2/repaglinide AUC0–9 h ratio (U/ng)4.7 ± 1.71.3 ± 0.6***2.3 ± 0.5***,††3.7 ± 0.9*,†††,‡‡‡5.2 ± 1.5†††,‡‡‡,¶¶¶
    -Fold (range)0.3 (0.1–0.4)0.5 (0.3–0.8)0.8 (0.6–1.2)1.1 (0.8–1.6)
M4
    Cmax (U/ml)9.4 ± 2.10.8 ± 0.5***7.4 ± 1.3*,†††9.8 ± 3.1†††,10.5 ± 3.9†††,
    -Fold (range)0.09 (0.04–0.16)0.8 (0.5–1.3)1.0 (0.5–1.5)1.1 (0.7–1.6)
    AUC0–3 h (U × h/ml)12.8 ± 5.11.4 ± 0.5***13.4 ± 2.4†††15.3 ± 5.5†††13.5 ± 5.7†††
    -Fold (range)0.11 (0.07–0.15)1.0 (0.6–1.8)1.2 (0.8–1.9)1.1 (0.8–1.5)
    M4/repaglinide AUC0–3 h ratio (U/ng)3.8 ± 1.10.09 ± 0.02***1.6 ± 0.4***,†††3.3 ± 0.8†††,‡‡‡3.8 ± 0.6†††,‡‡‡
    -Fold (range)0.02 (0.02–0.06)0.4 (0.2–0.8)0.9 (0.6–1.4)1.0 (0.7–1.8)
  • * P < 0.05 vs. control; ** P < 0.005 vs. control; *** P < 0.001 vs. control.

  • P < 0.05 vs. 1 h; †† P < 0.005 vs. 1 h; ††† P < 0.001 vs. 1 h.

  • P < 0.05 vs. 24 h; ‡‡ P < 0.005 vs. 24 h; ‡‡‡ P < 0.001 vs. 24 h.

  • P < 0.05 vs. 48 h; ¶¶ P < 0.005 vs. 48 h; ¶¶¶ P < 0.001 vs. 48 h.