Effects of cyclosporine on dose-normalized methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) enantiomer plasma concentrations after oral methadone in subjects receiving nothing (controls, 0.175 mg/kg methadone hydrochloride, open circles) or 4 days of cyclosporine (4.5 mg/kg twice per day), where the methadone hydrochloride dose was 0.14 mg/kg (closed circles). (A) R-methadone, (B) S-methadone, (C) R-EDDP, and (D) S-EDDP. Results are the mean ± standard deviation (N=16). Methadone and EDDP dose (enantiomer base)-normalized concentrations were significantly lower in cyclosporine-treated subjects between 1 and 3 hr after dosing (p<0.05).