Pharmacogenetic, Clinical, Prescribing, and Demographic Predictors of Sertraline Pharmacokinetics

Figures

• 

  Figure 1. Sertraline plasma concentrations across (A) CYP2C19, (B) CYP2B6, (C) CYP2D6, (D) CYP2C9, and (E) CYP3A4 genotype-predicted metabolizer groups. Footnotes: Genotype-predicted metabolizer status was indeterminate for 10 patients for CYP2D6 and for 1 patient for CYP2B6 and CYP3A4. Boxes represent the interquartile range (25th–75th percentiles), horizontal lines within boxes indicate medians, and whiskers extend from the minimum to the maximum observed values. Dots represent individual patient observations. Panels (A–D) were analyzed using the Kruskal–Wallis test, followed by Dunn’s multiple-comparisons test; panel (E) was analyzed using the Mann–Whitney U test. Overall p-values are shown in the upper-right corner of each panel, while brackets indicate significant pairwise comparisons with p-values. Subgroup sample sizes are provided below the corresponding x-axis labels.

• 

  Figure 2. Sertraline concentration-to-dose (C/D) across (A) CYP2C19, (B) CYP2B6, (C) CYP2D6, (D) CYP2C9, and (E) CYP3A4 genotype-predicted metabolizer groups. Footnotes: Genotype-predicted metabolizer status was indeterminate for 10 patients for CYP2D6 and for 1 patient for CYP2B6 and CYP3A4. Boxes represent the interquartile range (25th–75th percentiles), horizontal lines within boxes indicate medians, and whiskers extend from the minimum to the maximum observed values. Dots represent individual patient observations. Panels (A–D) were analyzed using the Kruskal–Wallis test, followed by Dunn’s multiple-comparisons test; panel (E) was analyzed using the Mann–Whitney U test. Overall p-values are shown in the upper-right corner of each panel, while brackets indicate significant pairwise comparisons with p-values. Subgroup sample sizes are provided below the corresponding x-axis labels.

• 

  Figure 3. Exploratory descriptive analysis of sertraline plasma concentrations across combined CYP2C19 and CYP2B6 genotype-predicted metabolizer groups. Footnote: CYP2C19 PM and CYP2B6 PM groups were defined according to CPIC genotype-predicted metabolizer classifications. Non-PM includes gIM, gNM, gRM, and gUM. Boxes represent the interquartile range (25th–75th percentiles), horizontal lines within boxes indicate medians, and whiskers extend from the minimum to the maximum observed values. Dots represent individual patient observations. Subgroup sample sizes are provided below the corresponding x-axis labels. Of the 11 patients with CYP2B6 gPM status but without CYP2C19 gPM status, 1, 7, and 3 were CYP2C19 gIMs, gNMs, and gRMs, respectively. Among the 136 patients who were non-poor metabolizers for both CYP2B6 and CYP2C19, 37, 64, 29, and 6 were CYP2C19 gIMs, gNMs, gRMs, and gUMs, respectively. Only 1 patient with unavailable CYP2B6 genotype-predicted metabolizer status was excluded from the combined-gene analysis.

• 

  Figure 4. Sertraline-to-norsertraline MR across (A) CYP2C19, (B) CYP2B6, (C) CYP2D6, (D) CYP2C9, and (E) CYP3A4 genotype-predicted metabolizer groups. Footnotes: Genotype-predicted metabolizer status was indeterminate for 10 patients for CYP2D6 and for 1 patient for CYP2B6 and CYP3A4. Boxes represent the interquartile range (25th–75th percentiles), horizontal lines within boxes indicate medians, and whiskers extend from the minimum to the maximum observed values. Dots represent individual patient observations. Panels (A–D) were analyzed using the Kruskal–Wallis test, followed by Dunn’s multiple-comparisons test; panel (E) was analyzed using the Mann–Whitney U test. Overall p-values are shown in the upper-right corner of each panel, while brackets indicate significant pairwise comparisons with p-values. Subgroup sample sizes are provided below the corresponding x-axis labels.

• 

  Figure 5. Sertraline concentrations and MR according to CYP2C:TG haplotype status within CYP2C19 genotype-predicted metabolizer groups. (A) Sertraline concentration and (B) MR. Footnotes: “+TG” denotes carriage of one CYP2C:TG haplotype, whereas “+TG/TG” denotes carriage of two copies. CYP2C19:TG haplotype status was indeterminate for two patients (one gNM and one gIM), who were excluded from the TG haplotype subgroup analysis. Boxes represent the interquartile range (25th–75th percentiles), horizontal lines within boxes indicate medians, and whiskers extend from the minimum to the maximum observed values. Dots represent individual patient observations. Subgroup sample sizes are provided below the corresponding x-axis labels.