Table 1.

Disposition of total (bound plus unbound) (R)- and (S)-methadone following chronic dosing of between 7.5 mg and 130 mg rac-methadone once daily in 18 patients enrolled in a maintenance programme.

Parameter1		Mean	Range	%CV	P value2 (mean difference; 95% CI)
${\mathrm{C}}_{\min \left(\mathrm{first}\right)}^{\mathrm{ss}}$ (ng ml−l)	(R)-methadone	147	42–223	30	0.55
	(S)-methadone	153	31–261	43	(−6; −24, 14)
${\mathrm{C}}_{\min \left(\mathrm{last}\right)}^{\mathrm{ss}}$ (ng ml−1)	(R)-methadone	148	40–243	34	0.78
	(S)-methadone	146	31–242	42	(2; −15, 20)
${\mathrm{C}}_{\max }^{\mathrm{ss}}$ (ng ml−1)	(R)-methadone	251	120–362	27	0.0002
	(S)-methadone	303	116–447	32	(−52; −74, −29)
${\mathrm{C}}_{\mathrm{av}}^{\mathrm{ss}}$ (ng ml−1)	(R)-methadone	168	67–237	29	0.0571
	(S)-methadone	186	52–304	37	(−18; −36, 1)
${\mathrm{AUC}}_{\tau }^{\mathrm{ss}}$ (ng ml−1 h)	(R)-methadone	3484	608–7263	53	0.21
	(S)-methadone	3797	589–7229	55	(−313; −814, 188)
CL/F (ml min−1)	(R)-methadone	161	103–363	42	0.86
	(S)-methadone	159	79–465	60	(2; −18, 21)
CLR (ml min−1)	(R)-methadone	27.4	11.9–46.6	37	< 0.0001
	(S)-methadone	15.1	7.0–26.5	39	(12.4; 9.2, 15.5)
CLMD→EDDP (ml min−1)	(R)-methadone	21.9	3.6–37.3	48	0.0088
	(S)-methadone	28.8	5.5–58.9	55	(−6.9; −11.6, 2.2)
P/T	(R)-methadone	1.81	1.35–3.58	30	< 0.0001
	(S)-methadone	2.30	1.68–4.49	34	(−0.49; −0.68, −0.29)

¹${\mathrm{C}}_{\min \left(\mathrm{first}\right)}^{\mathrm{ss}}$=plasma concentration, normalized to a 70 mg rac-methadone dose, predose; ${\mathrm{C}}_{\min \left(\mathrm{last}\right)}^{\mathrm{ss}}$=plasma concentration, normalized to a 70 mg rac-methadone dose, 24 h after dosing; ${\mathrm{C}}_{\max }^{\mathrm{ss}}$=maximum measured plasma concentration, normalized to a 70 mg rac-methadone dose; ${\mathrm{C}}_{\mathrm{av}}^{\mathrm{ss}}$=steady-state plasma concentration, normalized to a 70 mg rac-methadone dose; ${\mathrm{AUC}}_{\tau }^{\mathrm{ss}}$=area under the plasma concentration-time curve during the inter-dosing interval; CL/F = apparent plasma clearance at steady-state; CL_R=renal clearance; CL_MD→EDDP=apparent partial clearance of methadone to EDDP; P/T=peak to trough plasma concentration ratio.

²Comparison of (R)-methadone vs (S)-methadone.