Drug | Approximate Difference in Mean/Median Concentrations (AUC) Compared with *1 / *1, Unless Otherwise Stated | Evidence for Genotyping | Evidence against Genotyping | References for Pharmacokinetic Data |
---|---|---|---|---|
Amitriptyline | Single dose: 1.4- and 0.4-fold for amitriptyline and nortriptyline, respectively; repeated dosing: (Cpmin or Cp∼11 h) 1.8-fold (PM), cf. hom EM for amitriptyline (het EM similar to hom EM); 0.4-fold (PM); 0.8-fold (het EM), cf. hom EM for nortriptyline | Reciprocal change in parent to metabolite; multiple metabolic pathways to multiple active metabolites; little evidence for altered effect with CYP2C19 status | Shimoda et al. (2002); Jiang et al. (2003); Steimer et al. (2004) | |
Citalopram | Single dose: 1.2-fold; repeated dosing: 1.8- and 1.6-fold for racemic and S-citalopram, respectively; no difference in R-citalopram | Relatively wide therapeutic index; concentration-effect relationship ill-defined for the SSRIs | Sindrup et al. (1993); Herrlin et al. (2003); Yu et al. (2003) | |
Clomipramine | Single dose: 1.5-fold; repeated dosing (Cp∼13 h): 1.8-fold (PM), 1.4-fold (het EM), cf. hom EM | Multiple metabolic pathways to multiple active metabolites; little evidence for altered effect with CYP2C19 status; concentration-effect relationship ill-defined | Kramer Nielsen et al. (1994); Yokono et al. (2001) | |
Diazepam | Single dose: 1.3- to 4.3-fold and 1.9-fold for diazepam and desmethyldiazepam, respectively; 6.1- and 2.4-fold (PM), 2.5- and 1.4-fold (het EM), cf. hom EM for diazepam and desmethyldiazepam, respectively | Multiple metabolic pathways to multiple active metabolites; clinical studies lacking | Bertilsson et al. (1989); Zhang et al. (1990); Sohn et al. (1992b); Wan et al. (1996); Qin et al. (1999) | |
Fluoxetine | Single dose: 2.9- and 0.4-fold (PM), cf. hom EM for fluoxetine and norfluoxetine, respectively; 0.9-fold (het EM), cf. hom EM for norfluoxetine; nonsignificant increase in fluoxetine in het EM | Reciprocal changes suggest little overall effect; multiple metabolic pathways; clinical studies lacking | Liu et al. (2001) | |
Imipramine | Single dose: 1.4-fold; repeated dosing (Cp12 h): 1.7- to 2.4-, 0.6- to 1.0-fold (N.S. in some studies), and 1.8-fold for imipramine, desipramine and imipramine + desipramine, respectively | Multiple metabolic pathways to multiple active metabolites; little evidence for altered effect with CYP2C19 status; concentration-effect relationship ill-defined | Skjelbo et al. (1991); Koyama et al. (1994, 1996b); Morinobu et al. (1997) | |
Lansoprazole | Single dose: 4.6-fold; 3.7- to 5.6-fold (PM), 1.4- to 1.8-fold (het EM, N.S.), cf. hom EM; repeated dosing: 3.9- to 5.4-fold (PM), 1.7- to 2.4-fold (het EM), cf. hom EM | Treatment failure more likely in homozygous EMs | Very high therapeutic index | Sohn et al. (1997); Furuta et al. (2001c); Ieiri et al. (2001); Sakai et al. (2001); Kim et al. (2002); Shirai et al. (2002) |
Mephobarbital | Single-dose: 92- and 2.8-fold (PM), 4.4- and 1.3-fold (het EM, N.S.), cf. hom EM for R-mephobarbital and phenobarbital, respectively; no significant difference for S-mephobarbital | This seems to be a world record–more study is needed | Kobayashi et al. (2004) | |
Moclobemide | Single dose: 2.7-fold; 2.7- to 3.5-fold (PM), 1.3- to 1.7-fold (het EM), cf. hom EM; repeated dosing: 1.6-fold | High therapeutic index; saturable metabolism | Gram et al. (1995); Hoskins et al. (2000); Yu et al. (2001) | |
Omeprazole | Single dose: 5- to 12-fold; 6- to 20-fold (PM), 2- to 4-fold (het EM), cf. hom EM; repeated dosing: 4.4-fold; 7- to 13-fold (PM), 2- to 5-fold (het EM), cf hom EM | Treatment failure more likely in homozygous EMs | Very high therapeutic index | Andersson et al. (1992); Sohn et al. (1992a); Chang et al. (1995b); Yasuda et al. (1995a); Furuta et al. (1999b); Shirai et al. (2001); Cho et al. (2002) |
Pantoprazole | Single dose: 6.0-fold | Treatment failure more likely in homozygous EMs | Very high therapeutic index | Tanaka et al. (1997) |
Proguanil | Single dose: 1.5-fold for proguanil (cycloguanil less than 0.3-fold cf EM); repeated dosing: 0.5-fold for cycloguanil (active metabolite) | Evidence lacking for clinical effects | Helsby et al. (1993); Setiabudy et al. (1995); Thaper et al. (2002); Herrlin et al. (2000) | |
Rabeprazole | Single dose: 1.8-fold; 3.1- to 4.3-fold (PM); 1.3- to 2.3-fold (het EM, N.S. in all studies), cf hom EM; repeated dosing: 1.9-fold; 3.5- to 5.3-fold (PM); 1.7- to 3.0-fold (het EM, N.S. in all studies), cf. hom EM | Treatment failure more likely in homozygous EMs | Very high therapeutic index | Yasuda et al. (1995a); Horai et al. (2001); Ieiri et al. (2001); Shirai et al. (2001); Lin et al. (2003) |
Sertraline | Single dose: 1.4-fold | High therapeutic index; concentration-effect relationship ill-defined for the SSRIs | Wang et al. (2001) | |
Voriconazole | Repeated dosing: 3.8- to 5.8-fold | Clinical implications unclear | Ikeda et al. (2004) |
N.S., not significant