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. 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 5.

Oral 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 13 ± 3 13 ± 4 14 ± 5 23 ± 6 21 ± 7 24 ± 10
tmax, h 4 (3–6) 4 (3–10) 3 (2–10) 4 (2–6) 4 (3–10) 3 (2–10)
AUC0-96, ng · h ·ml−1) 461 ± 72 512 ± 123 482 ± 148 639 ± 165 645 ± 280 638 ± 326
AUC0-∞, ng · h−1 · ml−1) 571 ± 115 650 ± 160 578± 162 710 ± 185 728 ± 341 698 ± 363
AUC0-∞ ratio, ritonavir-indinavir/control 1.13 (0.99–1.29) 1.00 (0.89–1.12) 0.96 (0.80–1.15) 0.92 (0.78–1.08)
CL/F, ml · kg−1 · min−1 2.25 ± 0.54 2.00 ± 0.50 2.25 ± 0.53 1.87 ± 0.59 2.05 ± 0.94 2.14 ± 0.92
Elimination t1/2, h 39 ± 9 43 ± 11 37 ± 7 28 ± 5 29 ± 8 26 ± 5
Vz/F, l/kg 7.4 ± 1.6 7.3 ± 2.1 7.2 ± 1.8 4.4 ± 1.2 4.8 ± 1.9 4.6 ± 1.7
Foral 0.89 ± 0.12 0.97 ± 0.07 0.96 ± 0.07 0.88 ± 0.12 0.93 ± 0.06 0.92± 0.06
R-EDDP S-EDDP
Control Acute
Ritonavir/Indinavir		 Steady-state
Ritonavir/Indinavir		 Control Acute
Ritonavir/Indinavir		 Steady-state
Ritonavir/Indinavir
Cmax, ng/ml 1.6 ± 0.4 1.7 ± 0.5 1.9 ± 0.4 2.4 ± 0.7 3.0 ± 1.3 * 3.0 ± 0.9 *
AUC0-96, ng · h · ml−1 63 ± 11 69 ± 17 72 ± 18 87 ± 19 102± 18 * 104± 21 *
AUC∞, ng · h−1 ·ml−1 88 ± 18 119± 43 119± 43 107 ± 24 126± 20 * 129 ± 23
Elimination t1/2, h 50 ± 15 74 ± 28 66 ± 25 37 ± 6 41 ± 10 39 ± 9
AUC0-96, EDDP/methadone 0.14 ± 0.02 0.14 ± 0.03 0.16 ± 0.05 0.14 ± 0.04 0.19 ± 0.09 * 0.19 ± 0.09 *
AUC∞, EDDP/methadone 0.16 ± 0.03 0.19 ± 0.06 0.22 ± 0.11 0.16 ± 0.05 0.21 ± 0.10 * 0.22 ± 0.10 *
AUC∞ (EDDP/methadone) ratio, ritonavir-indinavir/control 1.15 (0.99–1.33) 1.30 (1.07–1.59) 1.24 (1.05–1.46) 1.33 (1.12–1.57)
*

Significantly different from control (P<0.05). AUC = area under the plasma concentration-time curve; Cmax = peak plasma concentration; CL/F = apparent oral clearance; EDDP = 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine; Foral = bioavailability; Vz/F = apparent volume of distribution.

Subjects received 11.0 mg oral methadone HCl at all sessions. Results are the arithmetic mean ± SD (n = 12), except the time to peak concentration (tmax), which is the median (and range), and the area under the concentration–time curve (AUC) ratio (ritonavir-indinavir/control), which is the geometric mean (90% CI).