Effect of CYP2D6 genotype on flecainide pharmacokinetics in Japanese patients with supraventricular tachyarrhythmia
- 232 Downloads
Erratum to: Eur J Clin Pharmacol 62:919–926DOI 10.1007/s00228-006-0188-x
Summary of analysis models for the pharmacokinetic parameters of flecainide
| Number | Model equation | OFV | ΔOFV | Comparison | P value* |
|---|---|---|---|---|---|
| 1 | \( V \mathord{\left/ {\vphantom {V {F = \theta _{1} \quad {CL} \mathord{\left/ {\vphantom {{CL} F}} \right. \kern-\nulldelimiterspace} F = \theta _{2} \cdot e^{{\eta i}} }}} \right. \kern-\nulldelimiterspace} {F = \theta _{1} \quad {CL} \mathord{\left/ {\vphantom {{CL} F}} \right. \kern-\nulldelimiterspace} F = \theta _{2} \cdot e^{{\eta i}} } \) | 816.0 | – | – | – |
| 2 | \( V \mathord{\left/ {\vphantom {V {F = \theta _{1} \quad {CL} \mathord{\left/ {\vphantom {{CL} {F = \theta _{2} \cdot WT^{{\theta _{3} }} \cdot e^{{\eta i}} }}} \right. \kern-\nulldelimiterspace} {F = \theta _{2} \cdot WT^{{\theta _{3} }} \cdot e^{{\eta i}} }}}} \right. \kern-\nulldelimiterspace} {F = \theta _{1} \quad {CL} \mathord{\left/ {\vphantom {{CL} {F = \theta _{2} \cdot WT^{{\theta _{3} }} \cdot e^{{\eta i}} }}} \right. \kern-\nulldelimiterspace} {F = \theta _{2} \cdot WT^{{\theta _{3} }} \cdot e^{{\eta i}} }} \) | 798.7 | 17.3 | vs 1 | P < 0.005 |
| 3 | \( V \mathord{\left/ {\vphantom {V {F = \theta _{1} \quad {CL} \mathord{\left/ {\vphantom {{CL} {F = \theta _{2} \cdot WT^{{\theta _{3} }} \cdot \theta ^{{AGE \geqslant 70}}_{4} \cdot e^{{\eta i}} }}} \right. \kern-\nulldelimiterspace} {F = \theta _{2} \cdot WT^{{\theta _{3} }} \cdot \theta ^{{AGE \geqslant 70}}_{4} \cdot e^{{\eta i}} }}}} \right. \kern-\nulldelimiterspace} {F = \theta _{1} \quad {CL} \mathord{\left/ {\vphantom {{CL} {F = \theta _{2} \cdot WT^{{\theta _{3} }} \cdot \theta ^{{AGE \geqslant 70}}_{4} \cdot e^{{\eta i}} }}} \right. \kern-\nulldelimiterspace} {F = \theta _{2} \cdot WT^{{\theta _{3} }} \cdot \theta ^{{AGE \geqslant 70}}_{4} \cdot e^{{\eta i}} }} \) | 779.0 | 19.7 | vs 2 | P < 0.005 |
| 4 | \( V \mathord{\left/ {\vphantom {V F}} \right. \kern-\nulldelimiterspace} F = \theta _{1} \quad {CL} \mathord{\left/ {\vphantom {{CL} F}} \right. \kern-\nulldelimiterspace} F = \theta _{2} \cdot WT^{{\theta _{3} }} \cdot \theta ^{{AGE \geqslant 70}}_{4} \cdot \theta ^{{SEX}}_{5} \cdot e^{{\eta i}} \) | 772.4 | 6.6 | vs 3 | P < 0.05 |
| 5 | \( V \mathord{\left/ {\vphantom {V F}} \right. \kern-\nulldelimiterspace} F = \theta _{1} \quad {CL} \mathord{\left/ {\vphantom {{CL} F}} \right. \kern-\nulldelimiterspace} F = \theta _{2} \cdot WT^{{\theta _{3} }} \cdot \theta ^{{AGE \geqslant 70}}_{4} \cdot \theta ^{{SEX}}_{5} \cdot Scr^{{\theta _{6} }} \cdot e^{{\eta i}} \) | 760.9 | 11.5 | vs 4 | P < 0.005 |
| 6 | \(\begin{aligned} & V \mathord{\left/ {\vphantom {V {F = \theta _{1} }}} \right. \kern-\nulldelimiterspace} {F = \theta _{1} } \\ & {CL} \mathord{\left/ {\vphantom {{CL} {F = \theta _{2} \cdot WT^{{\theta _{3} }} \cdot \theta ^{{AGE \geqslant 70}}_{4} }}} \right. \kern-\nulldelimiterspace} {F = \theta _{2} \cdot WT^{{\theta _{3} }} \cdot \theta ^{{AGE \geqslant 70}}_{4} } \cdot \theta ^{{SEX}}_{5} \cdot Scr^{{\theta _{6} }} \cdot {\left( {\theta _{E} \cdot EM + \theta _{I} \cdot IM + \theta _{P} \cdot PM} \right)} \cdot e^{{\eta i}} \\ \end{aligned} \) | 750.7 | 10.2 | vs 5 | P < 0.05 |
Final population pharmacokinetic parameter estimates for flecainide
| Parameter | Estimates | CV% |
|---|---|---|
| V/F (l) | ||
| V/F = θ 1 | ||
| θ 1 | 379.0 | 15.7 |
| CL/F (l/h) | ||
| \( {CL} \mathord{\left/ {\vphantom {{CL} F}} \right. \kern-\nulldelimiterspace} F = \theta _{2} \cdot WT^{{\theta _{3} }} \cdot \theta ^{{AGE \geqslant 70}}_{4} \cdot \theta ^{{SEX}}_{5} \cdot Scr^{{\theta _{6} }} \cdot {\left( {\theta _{E} \cdot EM + \theta _{I} \cdot IM + \theta _{P} \cdot PM} \right)} \) | ||
| θ 2 | 1.25 | 54.7 |
| θ 3 | 0.49 | 27.9 |
| θ 4 | 0.70 | 7.0 |
| θ 5 | 0.76 | 6.1 |
| θ 6 | −0.35 | 39.0 |
| θ E | 1.04 | 8.7 |
| θ I | 0.82 | 11.5 |
| θ P | 0.71 | 17.1 |
| Interpatient variability (%) CL/F | ||
| CL/F | 17.8 | 47.5 |
| Intrapatient variability (%) | 13.1 | 50.0 |