Clinical, Behavioral, and Methadone Concentration Characteristics_
| Variable | Categories | Duration of treatment | p-value | |||
|---|---|---|---|---|---|---|
| <1 year | 1–3 years | >3 years | Total | |||
| Mean (SD) | Mean (SD) | Mean (SD) | Mean (SD) | |||
| Initial methadone dose (mg/day) | 21.0 (8.6) | 21.3 (8.6) | 18.8 (4.7) | 19.9 (6.8) | 0.021 | |
| Maintenance methadone dose (mg/day) | 58.6 (27.2) | 51.0 (28.1) | 51.2 (29.1) | 53.3 (28.4) | 0.182 | |
| Serum methadone (ng/mL) | 285.1 (207.0) | 275.3 (230.7) | 235.0 (208.0) | 257.6 (212.6) | 0.124 | |
| CDR | 5.0 (3.2) | 5.4 (3.9) | 4.8 (3.2) | 6.6 (3.7) | 0.801 | |
Multivariable Regression Analysis of Factors Associated with Methadone Dose, Serum Methadone Concentration, and Concentration-to-Dose Ratio (CDR)_
| Factors | Maintenance methadone dose | Log (Serum methadone concentration) | Log (CDR) | |||
|---|---|---|---|---|---|---|
| Coef. | 95%CI | Coef. | 95%CI | Coef. | 95%CI | |
| Age (per year) | −0.15 | −0.65, 0.36 | 0.003 | −0.009, 0.014 | 0.008 | −0.003, 0.019 |
| Duration of treatment (vs < 1 yeara) | ||||||
| 1–3 years | −7.29 | −19.21, 4.62 | −0.012 | −0.313, 0.289 | −0.005 | −0.305, 0.294 |
| >3 years | −4.25 | −14.12, 5.62 | −0.120 | −0.334, 0.094 | −0.096 | −0.311, 0.119 |
| Initial dose (per mg/day) | 0.45 | −0.04, 0.95 | −0.001 | −0.023, 0.021 | −0.005 | −0.027, 0.016 |
| Maintenance dose (mg/day) | – | – | 0.019* | 0.015, 0.022 | −0.001 | −0.004, 0.002 |
| Genotype (Yes vs Noa) | ||||||
| *1/*1 | −18.13 | −60.07, 23.81 | −0.127 | −0.796, 0.542 | 0.054 | −0.682, 0.791 |
| *1/*2 | 12.78 | −8.33, 33.88 | 0.205 | −0.191, 0.602 | 0.165 | −0.211, 0.541 |
| *1/*4 | −18.05 | −43.21, 7.11 | −0.273 | −0.803, 0.256 | −0.285 | −0.830, 0.259 |
| *1/*6 | −26.33* | −51.97, −0.69 | −0.132 | −0.720, 0.455 | −0.135 | −0.722, 0.452 |
| *2/*4 | −26.67 | −54.75, 1.40 | −0.604 | −1.347, 0.139 | −0.373 | −1.038, 0.291 |
| *2/*6 | 2.59 | −23.88, 29.05 | −2.485* | −3.024, −1.947 | −2.595* | −3.145, −2.046 |
| *4/*4 | 0.23 | −34.14, 34.60 | −0.286 | −0.849, 0.278 | −0.230 | −0.797, 0.337 |
| *4/*6 | −10.92 | −34.16, 12.31 | −0.162 | −0.595, 0.271 | −0.159 | −0.603, 0.285 |
| *6/*6 | −16.58 | −42.71, 9.56 | −0.146 | −0.663, 0.371 | −0.106 | −0.640, 0.429 |
| *6/*9 | −9.86 | −41.05, 21.32 | −0.076 | −0.773, 0.620 | −0.088 | −0.738, 0.562 |
| OPRM1 (vs AAa) | ||||||
| AG | 4.04 | −4.68, 12.75 | −0.017 | −0.250, 0.215 | 0.003 | −0.224, 0.231 |
| GG | 2.81 | −9.32, 14.93 | 0.074 | −0.217, 0.366 | 0.086 | −0.188, 0.361 |
| R2 | 0.1062 | 0.4435 | 0.1114 | |||
Distribution of Genotype, Allele, and SNP by Duration of Methadone Treatment_
| Variable | Categories | Duration of treatment | p-value | |||
|---|---|---|---|---|---|---|
| <1 year | 1–3 years | >3 years | Total | |||
| N (%) | N (%) | N (%) | N (%) | |||
| CYP2B6 genotype | *1/*1 | 2 (3.9) | 1 (2.5) | 2 (1.9) | 5 (2.5) | 0.762 |
| *1/*2 | 4 (7.7) | 1 (2.5) | 4 (3.8) | 9 (4.5) | 0.424 | |
| *1/*4 | 14 (26.9) | 15 (37.5) | 37 (34.9) | 66 (33.3) | 0.499 | |
| *1/*6 | 5 (9.6) | 4 (10.0) | 10 (9.4) | 19 (9.6) | 0.995 | |
| *2/*4 | 3 (5.8) | 2 (5.0) | 8 (7.5) | 13 (6.6) | 0.827 | |
| *2/*6 | 0 (0.0) | 0 (0.0) | 1 (0.9) | 1 (0.5) | 0.647 | |
| *4/*4 | 5 (9.6) | 5 (12.5) | 7 (6.6) | 17 (8.6) | 0.501 | |
| *4/*6 | 17 (32.7) | 9 (22.5) | 21 (19.8) | 47 (23.7) | 0.198 | |
| *4/*9 | 5 (9.6) | 4 (10.0) | 10 (9.4) | 19 (9.6) | 0.995 | |
| *6/*6 | 5 (9.6) | 3 (7.5) | 15 (14.2) | 23 (11.6) | 0.466 | |
| *6/*9 | 0 (0.0) | 1 (2.5) | 4 (3.8) | 5 (2.5) | 0.365 | |
| Allele presence | Allele *1 | 25 (48.1) | 21 (52.5) | 53 (50.0) | 99 (50.0) | 0.915 |
| Allele *2 | 7 (13.5) | 3 (7.5) | 13 (12.3) | 23 (11.6) | 0.645 | |
| Allele *4 | 44 (84.6) | 35 (87.5) | 83 (78.3) | 162 (81.8) | 0.364 | |
| Allele *6 | 27 (51.9) | 17 (42.5) | 51 (48.1) | 95 (48.0) | 0.668 | |
| Allele *9 | 5 (9.6) | 5 (12.5) | 14 (13.2) | 24 (12.1) | 0.807 | |
| rs3745274 [516G>T] | GG | 25 (48.1) | 23 (57.5) | 55 (51.9) | 103 (52.0) | 0.375 |
| TT | 5 (9.6) | 4 (10.0) | 19 (17.9) | 28 (14.1) | ||
| GT | 22 (42.3) | 13 (32.5) | 32 (30.2) | 67 (33.8) | ||
| rs2279343 [785A>G] | AA | 3 (5.8) | 1 (2.5) | 3 (2.8) | 7 (3.5) | 0.597 |
| AG | 22 (42.3) | 21 (52.5) | 58 (54.7) | 101 (51.0) | ||
| GG | 27 (51.9) | 18 (45.0) | 45 (42.5) | 90 (45.5) | ||
| rs8192709 [64C>T] | CC | 45 (86.5) | 37 (92.5) | 93 (87.7) | 175 (88.4) | 0.645 |
| CT | 7 (13.5) | 3 (7.5) | 13 (12.3) | 23 (11.6) | ||
| OPRM1 | AA | 21 (40.4) | 9 (22.5) | 38 (35.8) | 68 (34.3) | 0.475 |
| AG | 23 (44.2) | 22 (55.0) | 49 (46.2) | 94 (47.5) | ||
| GG | 8 (15.4) | 9 (22.5) | 19 (17.9) | 36 (18.2) | ||