TABLE 3.
Population pharmacokinetic model parameters of para-aminosalicylic acid with covariate effects due to the NAT1*14, NAT1*3, and NAT2*5 alleles, gender, and concomitant efavirenz
| Parametera | Mean value (RSE %)b in final model |
|---|---|
| Structural model | |
| CL/F, liters/h | 8.14 (11.3) |
| Apparent V/F, liters | 48.9 (6.9) |
| Ktr, h−1 | 0.617 (10.2) |
| No. of transit compartments | 3 |
| Interindividual variability | |
| ωCL/F | 31.4 (36.9) |
| ωV/F | 25.2 (54.4) |
| ωKtr | 52.3 (35.1) |
| Interoccasion variability | |
| πCL/F | 32.2 (49.0) |
| πKtr | 44.7 (42.0) |
| Residual variability | |
| Proportional residual error | 0.142 (29.6) |
| Additive residual error, μg/ml | 10.2 (12.1) |
| Covariatesc | |
| Efavirenz on CL/F | 0.226 (65.5) |
| Gender on CL/F | 0.315 (40.3) |
| NAT1*3 allele on CL/F | −0.19 (56.3) |
| NAT1*14 allele on CL/F | −0.644 (26.2) |
| NAT2*5 allele on CL/F | −0.32 (35.0) |
| ΔOFV (from baseline model) | −92.633 |
a
Abbreviations: CL/F, oral clearance; V/F, volume of distribution; Ktr, transit rate constant; ωCL/F, interindividual % CV of CL/F; ωV/F, interindividual % CV of V/F; ωKtr, interindividual % CV of Ktr; πCL/F, interoccasion % CV of CL/F; πKtr, interoccasion % CV of Ktr; OFV, minimum objective function value.
b
RSE, relative standard error.
c
Covariate (Cov) relationships on CL/F are described by CL/Fi = CL/F × exp(θ1 × Cov1 + … + θj × Covj).