Table 3.
Measured AUC and Parameters Determined from Digitalized Data for Oral Doses of S-Methadone, a Low ERH Drug, in Healthy Volunteers Exhibiting Different CYP2B6 Genotypes and the Ratios of Parameters from the Study of Kharasch et al. [9]
| A. Absolute Values | ||||||||
|---|---|---|---|---|---|---|---|---|
| Genotype | N | Phenotype | Published AUC0→∞ ng/ml/hr | AUC0→96 ng/ml/hr | AUC0→∞ ng/ml/hr | t½,term, 1st dose hr | Cmax, 1st dose ng/ml | tmax hr |
| CYP2B6*1/*1 | 21 | Normal Metabolizers | 620 | 546.6 | 612.8 | 29.3 | 13.3 | 8.0 |
| CYP2B6*1/*6 | 20 | Intermediate Metabolizers | 734 | 630.1 | 714.9 | 30.8 | 19.1 | 3.0 |
| CYP2B6*6/*6 | 17 | Poor Metabolizers | 1242 | 887.8 | 1164.7 | 45.5 | 18.7 | 3.0 |
| CYP2B6*4/X (CYP2B6*1/*4 & CYP2B6*4/*6) | 4 | Rapid Metabolizers | 155 | 152.2 | 156.5 | 17.7 | 5.7 | 6.0 |
| B. Ratios versus Normal Metabolizers | ||||||||
| Genotype | N:N | Phenotype | Published AUC0→∞ | AUC0→96 | AUC0→∞ | t½, term, 1st dose | Cmax, 1st dose | tmax |
| CYP2B6*1/*6 | 20:21 | Intermediate Metabolizers | 1.2 | 1.2 | 1.2 | 1.1 | 1.4 | 0.4 |
| CYP2B6*6/*6 | 17:21 | Poor Metabolizers | 2.0 | 1.6 | 1.9 | 1.6 | 1.4 | 0.4 |
| CYP2B6*4/X (CYP2B6*1/*4 & CYP2B6*4/*6) | 4:21 | Rapid Metabolizers | 0.3 | 0.3 | 0.3 | 0.6 | 0.4 | 0.8 |