Table 1.
Demographic and pharmacokinetic (PK) characteristics for 57 children with the most commonly encountered CYP2C19 phenotypes, normal-metabolizer (NM) and intermediate- metabolizer (IM).
| Normal BMI (n=28) | Overweight BMI (n=16) | Obese BMI (n=13) | p-value* | |
|---|---|---|---|---|
| Age (years) | 13.7 ± 3.8 | 14.9 ± 2.6 | 12.7 ± 3.0 | 0.2 |
| BMI percentile for age | 62.0 ± 18.2 | 89.3 ± 2.5 | 97.7 ± 1.8 | 0.0001 |
| BMI z-score | 0.3 ± 0.5 | 1.3 ± 0.2 | 2.1 ± 0.4 | 0.0001 |
| Total Body Weight (TBW; kg) | 51.2 ± 17.5 | 65.9 ± 11.8 | 77.5 ± 28.7 | 0.0001 |
| Lean Body Weight (LBW; kg) | 38.8 ± 13.5 | 44.0 ± 9.6 | 48.1 ± 16.1 | 0.1 |
| Female | 50% | 69% | 60% | 0.2 |
| CYP2C19 NM | 82% | 75% | 69% | 0.3 |
| CYP2C19 IM | 18% | 25% | 31% | 0.3 |
| Ethnicity | ||||
| Caucasian | 72% | 88% | 53% | 0.2 |
| African American | 21% | 6% | 20% | 0.2 |
| Hispanic | 7% | 0 | 20% | 0.2 |
| Mixed | 0 | 6% | 7% | NA |
| Observed PK Parameters | ||||
| t1/2 (h) | 0.87 ± 0.3 | 1.04 ± 0.37 | 0.95 ± 0.32 | 0.7 |
| Tmax (h) | 0.73 ± 0.29 | 0.75 ± 0.26 | 0.54 ± 0.14 | 0.07 |
| Cmax (mcg/mL) | 1.81 ± 0.72 | 1.94 ± 0.71 | 2.68 ± 0.98 | 0.005 |
| AUC0–inf (mcg* h/mL) | 3.03 ± 1.92 | 3.25 ± 1.63 | 4.33 ± 2.61 | 0.2 |
| CL/F (L/h) | 20.4 ± 14.2 | 18.7 ± 7.43 | 16.8 ± 8.55 | 0.6 |
| Vd/F (L) | 30.1 ± 21.5 | 30.2 ± 12.3 | 22.8 ± 10.1 | 0.4 |
| Adjusted PK Parameters | ||||
| adjCmax (mcg/mL per mg/kg TBW) | 2.03 ± 0.92 | 2.46 ± 0.93 | 3.52 ± 1.13 | 0.0001 |
| adjAUC0–inf (mcg* h/mL per mg/kg TBW) | 3.45 ± 2.48 | 4.23± 2.61 | 5.82 ± 3.86 | 0.04 |
| adjCL/F (L/h/kg TBW) | 0.42 ± 0.27 | 0.29 ± 0.12 | 0.23 ± 0.13 | 0.03 |
| adjVd/F (L/kg TBW) | 0.59 ± 0.36 | 0.46 ± 0.2 | 0.3 ± 0.1 | 0.008 |
PK parameters are reported for single oral dose administration of pantoprazole, 1.2mg/kg lean body weight (LBW), as values unadjusted (i.e., raw/observed) and adjusted (adj) for total body weight (TBW);
*
p-values provided for comparisons between children with normal weight vs. obesity.