Table 4.
Factors influencing metformin pharmacokinetic parameters. Results from the multivariate analysis.
| Pharmacokinetic Parameters | ||||||||
|---|---|---|---|---|---|---|---|---|
| Independent Variable | AUC (ng·h/mL) |
AUC/dW (ng·h·kg/mL·mg) |
Cmax (ng/mL) |
Cmax/dW (ng·kg/mL·mg) |
Tmax (h) | T1/2 (h) | Vd/F (L/kg) | Cl/F (L/h·kg) |
| Sex | --- | −168.9 (−228.3, −109.5) | --- | −14.6 (−21.9, −7.4) | −0.5 (−0.9, −0.1) | 0.5 (0.3, 0.7) | 2358.6 (1545.5, 3171.7) | 274.2 (163.0, 385.4) |
| Age | 94.6 (47.8, 414.4) | 9.7 (5.9, 13.4) | 12.3 (6.7, 18.0) | 1.0 (0.6, 1.5) | --- | --- | −89.4 (−140.6, −38.1) | −9.4 (−16.0, −2.7) |
| Ethnicity | --- | −126.9 (−190.3, −63.4) | --- | −14.9 (−22.7, −7.2) | --- | --- | 975.9 (132.3, 1819.4) | --- |
| ABCG2 rs2231142 | --- | --- | --- | 7.4 (0.3, 14.4) | --- | --- | --- | --- |
| SLC22A1 rs72552763 | --- | --- | 74.4 (2.7, 146.0) | --- | --- | --- | --- | --- |
| SLC22A3 rs3088442 | --- | −53.3 (−96.9, −9.6) | --- | --- | --- | 0.1 (0.0, 0.3) | 762.7 (165.2, 1360.2) | 110.9 (31.0, 190.8) |
| SLC22A4 rs272893 | 716.8 (126.7, 1306.8) | --- | --- | --- | --- | --- | --- | --- |
| SLC22A4 rs1050152 | −57.9 (−103.9, −11.9) | --- | −6.2 (−11.8, −0.6) | --- | --- | --- | --- | |
| SLC47A2 rs12943590 | −658.7 (−1280.2, −37.3) | --- | --- | --- | --- | --- | --- | --- |
| R2 | 0.558 | 0.331 | 0.124 | 0.239 | 0.038 | 0.209 | 0.250 | 0.176 |
Abbreviation: Values shown as β (non-standardized β coefficient) expressed as number (CI 95%); AUC, area under the curve; Cmax, maximum plasma concentration; Tmax, time to reach the maximum plasma concentration; T1/2, half-life; Cl/F, total drug clearance adjusted for bioavailability; Vd/F, volume of distribution adjusted for bioavailability; dW, adjusted for dose and weight ratio.