Table 1.

Demographic characteristics of 59 methadone maintenance subjects studied for population pharmacokinetic analysis

	Model Development dataset	Model Validation dataset	Full data set	Significance
Number of subjects	38	21	59
Protocol 1*	33	20	53
Protocol 2†	5	1	6	0.41‡
Number of observations	463	262	725
Protocol 1*	432	246	678
Protocol 2†	31	16	47
Number of observationsper subject	11.8 ± 2.2 (7–13)	12.1 ± 1.7 (8–13)	11.9 ± 2.0 (7–13)	0.77§
Protocol 1*	12.9 ± 0.3 (12–13)	12.5 ± 1.1 (10–13)	12.8 ± 0.7 (10–13)
Protocol 2†	7.8 ± 0.5 (7–8)	8	7.8 ± 0.7 (7–8)
Age (years)	36 ± 8 (20–47)	32 ± 7 (21–48)	34 ± 8 (20–48)	0.12§
Weight (kg)	74 ± 15 (47–110)	69 ± 12 (44–87)	72 ± 14 (45–110)	0.32§
Sex (% male/% female)	71/39	48/52	63/37	0.09‡
α1-acid glycoprotein (mg. dl−1)	103 ± 23 (67–157)	112 ± 24 (73–160)	109 ± 23 (67–160)	0.30§
Dose/day (mg day−1)	76 ± 35 (7.5–150)	74 ± 44 (20–160)	76 ± 38 (7.5–160)	0.67§
Dose/day (mg kg−1 day−1)	1.1 ± 0.5 (0.1–2.2)	1.1 ± 0.7 (0.3–2.5)	1.1 ± 0.6 (0.1–2.5)	0.88§
Rac-methadone MR¶			1.7 ± 0.8 (0.5–4.1)**
(R)-methadone MR¶			1.2 ± 0.9 (0.3–5.3)
(S)-methadone MR¶			2.8 ± 1.4 (0.7–6.3)**
Subjects with urinalysis positive for the following (%)
Benzodiazepines	50	43	48	0.09‡
Barbiturates	0	1	1
Opiates	40	20	32	0.15‡
Sympathomimetic amines	11	10	10	0.99‡
Subjects with the following withdrawal status (%)
‘Dose not holding’	60	62	61	0.99‡

Data are presented as mean ± SD (range).

^*Blood sampling protocol 1 (13 samples taken over the interdosing interval).

^†Blood sampling protocol 2 (eight samples taken over the interdosing interval).

^‡Fisher's exact test for comparison of Model Development and Validation datasets.

^§Mann–Whitney U-test for comparison of Model Development and Validation datasets.

^¶Metabolic ratio: ratio of EDDP/methadone concentration in pooled 24 h urine sample (n = 37).

^**Significantly different from (R)-methadone metabolic ratio (MR) (P < 0.0001).