. 2021 Sep 17;12:726669. doi: 10.3389/fphar.2021.726669

TABLE 5.

Multivariate analysis of the differences in AUC_0-last, C_max, and T_1/2 between three groups of participants.

Multivariate model	Midazolam	Dabigatran	Pitavastatin^a	Pitavastatin lactone^a	Atorvastatin^a	4-Hydroxy atorvastatin^a	Rosuvastatin^b
N	53	53	52	52	52	52	29
AUC_0-last
Healthy young adults	1.00	1.00	1.00	1.00	1.00	1.00	1.00
Healthy elderly	2.19 (1.61–2.98)**	1.48 (1.06–2.05)*	0.99 (0.79–1.25)	1.25 (0.99–1.57)	2.00 (1.41–2.85)**	1.54 (1.10–2.14)*	2.02 (1.16–3.51)*
Elderly with CKD	2.68 (1.95–3.68)**	3.80 (2.72–5.31)**	1.57 (1.26–1.97)**	2.16 (1.70–2.74)**	4.15 (2.62–5.32)**	2.55 (1.82–3.56)**	2.09 (1.26–3.49)*
Elderly with CKD vs Healthy elderly	1.22 (0.89–1.67)	2.58 (1.85–3.59)**	1.59 (1.26–2.01)**	1.73 (1.37–2.18)**	1.86 (1.30–2.66)*	1.66 (1.17–2.34)*	1.04 (0.57–1.88)
Body weight	–	–	–	0.98 (0.98–0.99)**	–	–	–
Albumin	–	–	0.64 (0.41–1.00)*	–	–	–	–
Total bilirubin	–	–	–	0.79 (0.64–0.99)*	–	–	–
C_max
Healthy young adults	1.00	1.00	1.00	1.00	1.00	1.00	1.00
Healthy elderly	1.83 (1.40–2.38)**	1.30 (0.99–1.71)	1.02 (0.80–1.31)	1.06 (0.89–1.27)	2.15 (1.41–3.27)*	1.32 (0.97–1.79)	1.69 (1.11–2.55)*
Elderly with CKD	1.86 (1.42–2.44)**	1.91 (1.43–2.56)**	1.78 (1.38–2.30)**	1.63 (1.35–1.96)**	3.98 (2.61–6.08)**	1.71 (1.26–2.33)*	1.92 (1.28–2.87)*
Elderly with CKD vs Healthy elderly	1.02 (0.77–1.34)	1.47 (1.10–1.96)*	1.74 (1.36–2.24)**	1.53 (1.28–1.84)**	1.85 (1.21–2.83)*	1.30 (0.94–1.79)	1.14 (0.73–1.78)
Body weight	–	0.98 (0.97–0.99)**	0.98 (0.97–0.99)**	0.98 (0.98–0.99)**	–	–	0.98 (0.97–0.99)*
T_1/2
Healthy young adults	1.00	1.00
Healthy elderly	2.31 (1.72–3.10)**	1.15 (0.93–1.44)
Elderly with CKD	2.52 (1.89–3.36)**	2.93 (2.35–3.64)**
Elderly with CKD vs Healthy elderly	1.09 (0.80–1.48)	2.54 (2.01–3.19)**

Data are presented in the geometric mean ratio (95% confidence interval).

Variables with a p-value < 0.1 in the univariate analysis were included in the multivariable analysis.

A subject with SLCO1B1 wild-type’s plasma drug concentration was an outlier and was excluded from the model.

Twenty four subjects with ABCG2 variants (rs2231142, 421AA and 421CA) were excluded from the model.

*p < 0.05, **p < 0.001.

AUC_0-last: area under the concentration-time curve of time zero to the last time point; C_max: maximum plasma concentration; CKD: chronic kidney disease; T_1/2: half-life.