Table 4.
Patient demographics and pharmacokinetic parameter estimates.
| Parameter | Wild-type (*1/*1) | Heterozygotes | Homozygotes | p-value (ANOVA) |
|---|---|---|---|---|
| Subjects (n) | 85 | 52 | 9 | |
| Age (years) | 9.2 ± 2.6 | 9.4 ± 2.6 | 8.7 ± 2.2 | 0.72 |
| Weight (kg) | 40.0 ± 15.1 | 39.9 ± 14.5 | 33.1 ± 8.4 | 0.39 |
| Sex(M/F) | 35/50 | 21/31 | 4/5 | |
| Race (Cau/AA/others) | 62/21/2 | 42/7/3 | 9/0/0 | |
| OSA (yes/no) | 42/43 | 29/23 | 5/4 | |
| Bayesian estimates with the weight-based model † | ||||
| CL (l/min) for all | 1.22 ± 0.18 | 1.25 ± 0.20 | 1.10 ± 0.11‡‡,* | 0.013 |
| CL (l/min) for Cau (n) | 1.21 ± 0.17 (62) | 1.24 ± 0.15 (42) | 1.10 ± 0.11 (9)‡‡,* | 0.022 |
| Bayesian estimates with the final genotype model † | ||||
| CL (l/min) for all | 1.22 ± 0.16 | 1.26 ± 0.13 | 1.02 ± 0.09‡‡‡,*** | <0.001 |
| CL (l/min) for Cau (n) | 1.21 ± 0.16 (62) | 1.24 ± 0.14 (42) | 1.02 ± 0.09 (9)‡‡‡,*** | <0.001 |
Data are shown as mean ± standard deviation.
†
Allometric scaling of bodyweight with exponents of 0.75 and 1.0 for clearance (CL and Q) and volume of distribution (V1 and V2), respectively (see Table 3). Individual Bayesian clearance estimates were compared among the three OCT1 genotypes after they were standardized to an individual weighing 70 kg.
*
p < 0.05,
**
p < 0.01,
***
p < 0.001 versus wild-type,
‡
p < 0.05,
‡‡
p < 0.01,
‡‡‡
p < 0.001 versus heterozygotes (nonparametric comparisons for each pair using the Wilcoxon test).
AA: African–American; Cau: Caucasian; CL: Clearance; F: Female; M: Male; OSA: Obstructive sleep apnea.