Estimated metformin plasma steady-state pharmacokinetic parameters throughout gestation in subjects treated with 500 mg of metformin twice daily
The estimated pharmacokinetic parameters were compared between the early, mid, or late pregnancy study days and the postpartum study day. Data are means ± S.D.
| Parameter | Early Pregnancy (10–14 Weeks, n = 5) | Mid Pregnancy (22–26 Weeks, n = 7) | Late Pregnancy (34–38 Weeks, n = 4)a | Postpartum (n = 6) |
|---|---|---|---|---|
| Area under the concentration-time curve (ng · h/ml) | 6544 ± 2834 (N.S.) | 6144 ± 3381 (P < 0.05) | 6937 ± 1839 | 9804 ± 3140 |
| Time to maximal concentration (h) | 1.4 ± 0.2 (N.S.) | 2.0 ± 0.7 (N.S.) | 2.0 ± 0.7 | 1.8 ± 0.3 |
| Maximal concentration (ng/ml) | 1218 ± 465 (N.S.) | 1063 ± 485 (P < 0.05) | 1135 ± 304 | 1611 ± 386 |
| Apparent oral clearance (ml/min) | 1457 ± 560 (N.S.) | 1629 ± 648 (P < 0.05) | 1283 ± 418 | 928 ± 285 |
| Apparent oral clearance (ml/min/kg) | 15.1 ± 4.1 (N.S.) | 16.6 ± 5.4 (P < 0.05) | 11.9 ± 3.7 | 10.7 ± 2.7 |
| Renal clearance (ml/min) | 524 ± 221 (N.S.) | 710 ± 276 (P < 0.05) | 549 ± 63 | 415 ± 147 |
| Renal clearance (ml/min/kg) | 5.5 ± 1.9 (N.S.) | 7.3 ± 2.7 (P < 0.05) | 5.1 ± 0.5 | 4.7 ± 1.4 |
| Percentage of dose recovered in the urine unchanged (%) | 37 ± 12 (N.S.) | 44 ± 6 (N.S.) | 46 ± 14 | 45 ± 5 |
| Apparent oral volume of distribution (liters) | 509 ± 213 (P < 0.05) | 542 ± 229 (P < 0.05) | 432 ± 168 | 303 ± 66 |
| Apparent oral volume of distribution (l/kg) | 5.3 ± 1.8 (N.S.) | 5.6 ± 2.1 (N.S.) | 4.0 ± 1.5 | 3.6 ± 1.2 |
N.S., not significant.
↵a Because of the small number of subjects in late pregnancy, statistical comparisons were not performed for this study day.