Table 1.
Population demographics for metformin pediatric pharmacokinetic studies.
| Non-overweight a | Overweight / obesity b | Severe obesity, insulin resistant c |
|
|---|---|---|---|
| n | 6 | 22 | 30 |
| Dose (mg) | 850, qd (n=5) | 1,000, bid (n=19) | 1,000, bid (n=28) |
| 425, qd (n=1) | 500, bid (n=3) | 500, bid (n=2) | |
| Formulation | Immediate-release tablet | Immediate-release tablet | Immediate-release tablet d |
| PK study | |||
| Prandial state | Fed | Fasted e | Fasted e |
| Steady state | Yes | Yes | Yes |
| Duration, h | 12 | 8 | 12 |
| Population | Northern Spanish / Catalan (Barcelona, Spain) | White ('s-Hertogenbosch, the Netherlands) | 57% White, 40% African American, 3% Asian (United States); 10% Hispanic / Latino |
| Age, y | 9.5 (9.3 – 9.9) | 14 (11 – 18) | 11 (7.7 – 14) |
| Weight, kg | 33.3 (23.0 – 40.7) | 79.3 (54.7 – 105) | 77.0 (50.5 – 118) |
| Female, % | 100 | 73 | 57 |
| BMI, kg/m2 | 18.5 (15.7 – 21.0) | 29.1 (22.9 – 39.3) | 33.5 (24.2 – 43.6) |
| eGFR, mL/min/1.73 m2 | -- | 112 (94.1 – 136) f | 129 (91.7 – 188) g |
Data are expressed as mean (range) for continuous variables.
Clinical trial (isrctn.com ISRCTN49334271) in non-overweight girls with history of low birth weight and early-normal onset of puberty who were receiving 850 mg/day for 8 months; for the PK study, all girls received 850 mg metformin with dinner, except for 1 girl who accidentally received half that dose (425 mg).12
Clinical study (ClinicalTrials.gov NCT01487993) in 22 adolescents classified as either overweight or obese receiving 1,000 mg (or 500 mg for three subjects) of metformin twice daily for 37 weeks; blood samples for the PK study were collected during an oral glucose tolerance test.13
Six-month clinical trial (ClinicalTrials.gov NCT00005669) in children and adolescents with severe obesity receiving 1,000 mg (or 500 mg for two patients) of metformin; blood samples for the PK study were collected during a hyperglycemic clamp.14
Metformin capsules were manufactured and packaged by the National Institutes of Health Pharmaceutical Development Section.
Pharmacokinetic study was performed during a glucose tolerance test.
Published values were calculated using the Bedside Schwartz Equation
Published values were calculated using the CKiD Schwartz Equation.
bid, twice daily; BMI, body mass index; eGFR, estimated glomerular filtration rate; PK, pharmacokinetic; qd, once daily.