TABLE 2

Oral methadone pharmacokinetic parameters

Subjects received 11.0 mg oral methadone HCl at all sessions. Results are the arithmetic mean ± S.D., except area under the plasma concentration-time curve (AUC) ratios (ritonavir-lopinavir/control), which are the geometric mean (90% confidence interval). n = 12, except renal clearances and EDDP formation clearances (n = 10, due to incomplete urine collections in two subjects).

R-methadoneS-methadone
ControlAcute Ritonavir-LopinavirSteady-State Ritonavir-LopinavirControlAcute Ritonavir-LopinavirSteady-State Ritonavir-Lopinavir
Cmax (ng/ml)14 ± 68 ± 4*10 ± 4*23 ± 1010 ± 7*15 ± 8*
tmax (h)5 ± 36 ± 65 ± 25 ± 36 ± 55 ± 3
AUC0–96 (ng ⋅ h ⋅ ml−1)462 ± 154288 ± 201*399 ± 190690 ± 289324 ± 285*525 ± 332*
AUC0–∞ (ng ⋅ h ⋅ ml−1)672 ± 253424 ± 292*583 ± 301862 ± 404415 ± 397*688 ± 435
AUC0–∞ ratio (ritonavir-lopinavir/control)0.52 (0.38, 0.70)0.79 (0.61, 1.02)0.35 (0.24, 0.50)0.70 (0.50, 0.97)
CL/F (ml ⋅ kg−1 ⋅ min−1)1.98 ± 0.744.94 ± 4.70*2.81 ± 1.78*1.70 ± 0.906.48 ± 5.83*3.04 ± 3.16
Renal clearance (ml ⋅ kg−1 ⋅ min−1)0.15 ± 0.110.15 ± 0.150.16 ± 0.150.09 ± 0.060.11 ± 0.120.11 ± 0.09
Elimination t1/2 (h)50 ± 954 ± 2949 ± 2435 ± 836 ± 1440 ± 16
Vz/F (l/kg)8.4 ± 3.619.5 ± 15.4*10.0 ± 4.24.9 ± 2.617.5 ± 14.3*8.2 ± 5.4
Foral0.88 ± 0.200.79 ± 0.350.92 ± 0.240.87 ± 0.200.72 ± 0.310.92 ± 0.21
R-EDDPS-EDDP
ControlAcute Ritonavir-LopinavirSteady-State Ritonavir-LopinavirControlAcute Ritonavir-LopinavirSteady-State Ritonavir-Lopinavir
Cmax (ng/ml)1.4 ± 0.91.0 ± 0.51.4 ± 1.12.0 ± 1.51.8 ± 1.21.9 ± 1.1
AUC0–96 (ng ⋅ h ⋅ ml−1)46 ± 2230 ± 1439 ± 1370 ± 3654 ± 27 a63 ± 17 a
AUC (ng ⋅ h ⋅ ml−1)64 ± 4040 ± 2248 ± 1896 ± 6163 ± 30 a74 ± 21
Elimination t1/2 (h)43 ± 1236 ± 1436 ± 940 ± 1735 ± 2531 ± 6
AUC0–96 (EDDP/methadone)0.10 ± 0.030.12 ± 0.070.11 ± 0.050.11 ± 0.050.20 ± 0.140.19 ± 0.17
AUC (EDDP/methadone)0.10 ± 0.040.12 ± 0.070.10 ± 0.050.12 ± 0.050.21 ± 0.15*0.18 ± 0.17*
AUC0–96 (EDDP/methadone) ratio (ritonavir-lopinavir/control)1.16 (0.92,1.45)1.11 (0.95,1.29)1.74 (1.32, 2.31)1.46 (1.19,1.78)
EDDP formation clearance (ml ⋅ kg−1⋅ min−1)0.16 ± 0.100.17 ± 0.130.18 ± 0.100.20 ± 0.120.36 ± 0.300.28 ± 0.13
  • CLF, apparent oral clearance; Foral, bioavailability; t1/2, half-time.

  • * Significantly different from control (P < 0.05).