Skip to main content
. Author manuscript; available in PMC: 2011 Jun 9.
Published in final edited form as: Anesthesiology. 2009 Mar;110(3):660–672. doi: 10.1097/ALN.0b013e3181986a9a

Table 4.

Intravenous Methadone Pharmacokinetic Parameters.

R-methadone S-methadone
Control Acute
Ritonavir/Indinavir		 Steady-state
Ritonavir/Indinavir		 Control Acute
Ritonavir/Indinavir		 Steady-state
Ritonavir/Indinavir
Cmax, ng/ml 64 ± 40 50 ± 20 60 ± 26 90 ± 53 69 ± 26 80 ± 33
AUC0-96, ng · h−1 · ml−1) 290 ± 31 277 ± 83 279 ± 78 401 ± 81 353 ± 150 377 ± 170
AUC0-∞, ng · h−1 · ml−1 347 ± 43 345 ± 105 326 ± 83 436 ± 91 390 ± 178 406 ± 185
AUC0-∞ ratio, ritonavir-indinavir/control 0.96 (0.81–1.13) 0.92 (0.83–1.03) 0.83 (0.69–1.00) 0.88 (0.76–1.01)
CLIV, ml · kg−1 · min−1 1.98 ± 0.38 2.15 ± 0.82 2.15 ± 0.49 1.62 ± 0.44 2.04 ± 0.86 1.93 ± 0.78
CLH, ml · kg−1 · min−1 1.42 ± 0.29 1.32 ± 0.35 1.57 ± 0.40 † 1.26 ± 0.35 1.47 ± 0.64 1.55 ± 0.67
Elimination t1/2, h 37 ± 7 42 ± 14 36 ± 7 27 ± 4 27 ± 6 25 ± 5
Vss, L/kg 5.9 ± 1.4 7.2 ± 2.5 6.3 ± 1.8 3.4 ± 0.9 4.2 ± 1.6 3.8 ± 1.4
EH 0.09 ± 0.02 0.09 ± 0.02 0.10 ± 0.03 † 0.08 ± 0.02 0.10 ± 0.04 0.10 ± 0.04
R-EDDP S-EDDP
Control Acute
Ritonavir/Indinavir		 Steady-state
Ritonavir/Indinavir		 Control Acute
Ritonavir/Indinavir		 Steady-state
Ritonavir/Indinavir
Cmax, ng/ml 0.35 ± 0.08 0.29 ± 0.11 0.37 ± 0.11 † 0.73 ± 0.13 0.78 ± 0.27 0.86 ± 0.17
AUC0-96, ng · h−1 · ml−1 14 ± 6 15 ± 7 16 ± 8 32 ± 8 35 ± 11 37 ± 10
AUC∞, ng · h−1 · ml−1) 19 ± 8 26 ± 10 21 ± 10 39 ± 10 42 ± 12 44 ± 10
Elimination t1/2, h 28 ± 12 50 ± 19 * 32 ± 8 † 29 ± 6 31 ± 10 29 ± 6
AUC0-96, EDDP/methadone 0.05 ± 0.02 0.05 ± 0.02 0.06 ± 0.03 0.08 ± 0.03 0.11 ± 0.05 * 0.11 ± 0.05 *
AUC∞, EDDP/methadone 0.06 ± 0.03 0.07 ± 0.02 0.07 ± 0.03 0.10 ± 0.04 0.12 ± 0.06 * 0.12 ± 0.05 *
AUC∞ (EDDP/methadone) ratio, ritonavir-indinavir/control) 1.17 (0.88–1.55) 1.23 (0.96–1.56) 1.23 (1.07–1.41) 1.27 (1.11–1.45)
*

Significantly different from control (P < 0.05),

†

Significantly different from acute ritonavir-indinavir (P < 0.05). AUC = area under the plasma concentration-time curve; Cmax = peak plasma concentration; CLH = hepatic clearance; CLIV = systemic clearance; EDDP = 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine; EH = hepatic extraction; Vss = steady-state volume of distribution.

Subjects received 6.0 mg of IV methadone HCl at all sessions. Results are the arithmetic mean ± SD (n = 12), except area under the concentration-time curve (AUC) ratios (ritonavir-indinavir/control), which are the geometric mean (90% confidence interval).