TABLE 2.
Models explored to determine the influence of covariates on atazanavir pharmacokinetic parameters following genotype variant analysisa
| Covariate or genotype variant analysis | Model | θ0 | θ1 | θ2 | ΔOFV | P value |
|---|---|---|---|---|---|---|
| Covariate | ||||||
| Influence of sex on CL/F | CL = θ0 × (1 + θ1·sex) | 18.5 | 1.00 | 0.01 | NS | |
| Influence of wt on CL/F | CL = θ0 + θ1 × (wt-76) | 11.2 | −0.02 | −2.6 | NS | |
| Influence of age on CL/F | CL = θ0 + θ1 × (age-44) | 14.5 | −0.42 | 0.45 | NS | |
| Influence of TDF on CL/F | CL = θ0 × (1 + θ1·TDF) | 18.5 | 0.03 | 0.23 | NS | |
| Genotype variant analysis | ||||||
| Rich equation: influence of Het and Mut on CL/F | CL = θ0 + θ1·Het + θ2·Mut | 17.6 | −0.20 | 3.04 | 10.50 | <0.01 |
| Reduced equation 1: influence of Het on CL/F | CL = θ0 + θ1·(Het + Mut) | 18.5 | 1.21 | −37 | NS | |
| Reduced equation 2: influence of Mut on CL/F | CL = θ0 + θ2·Mut | 17.5 | 3.18 | 10.42 | <0.01 | |
| Linear equation, n = 0, 1, 2 | CL = θ0 + θ1·n | 18.5 | −0.46 | 0.13 | NS | |
| Power equation, n = 0, 1, 2 | CL = θ0 + θ1n | 18.0 | 0.71 | −29 | NS | |
| Square root equation, n = 0, 1, 2 | CL = θ0 + θ1·√n | 19.0 | −0.02 | −29 | NS |
a
CL/F, apparent oral clearance; θ0, typical value of the parameter; θ1 and θ2, estimates of the factor associated with the covariate; ΔOFV, change in objective function value; TDF, tenofovir; Het, heterozygous C/T alleles; Mut, homozygous T mutated alleles; NS, not statistically significant.