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Author: Admin | 2025-04-28
Fasting f Elderly subjects, mean age 71 years (range 65-81 years) g CLcr = creatinine clearance normalized to body surface area of 1.73 m 2 Subject Groups: Metformin hydrochloride tablets dose a (number of subjects) C max b (mcg/mL) T max c (hrs) Renal Clearance (mL/min) Healthy, nondiabetic adults: 500 mg single dose (24) 850 mg single dose (74) d 850 mg three times daily for 19 doses e (9) 1.03 (±0.33) 1.60 (±0.38) 2.01 (±0.42) 2.75 (±0.81) 2.64 (±0.82) 1.79 (±0.94) 600 (±132) 552 (±139) 642 (±173) Adults with type 2 diabetes mellitus: 850 mg single dose (23) 850 mg three times daily for 19 doses e (9) 1.48 (±0.5) 1.90 (±0.62) 3.32 (±1.08) 2.01 (±1.22) 491 (±138) 550 (±160) Elderly f , healthy nondiabetic adults: 850 mg single dose (12) 2.45 (±0.70) 2.71 (±1.05) 412 (±98) Renal-impaired adults: 850 mg single dose Mild (CLcr g 61 to 90 mL/min) (5) Moderate (CLcr 31 to 60 mL/min) (4) Severe (CLcr 10 to 30 mL/min) (6) 1.86 (±0.52) 4.12 (±1.83) 3.93 (±0.92) 3.20 (±0.45) 3.75 (±0.50) 4.01 (±1.10) 384 (±122) 108 (±57) 130 (±90) Pediatrics After administration of a single oral metformin hydrochloride 500 mg tablet with food, geometric mean metformin C max and AUC differed less than 5% between pediatric type 2 diabetic patients (12-16 years of age) and gender-and weight-matched healthy adults (20-45 years of age), all with normal renal function. Gender Metformin pharmacokinetic parameters did not differ significantly between normal subjects and patients with type 2diabetes mellitus when analyzed according to gender (males=19, females=16). Race No studies of metformin pharmacokinetic parameters according to race have been performed. Drug Interactions In Vivo Assessment of Drug Interactions Table 5: Effect of Coadministered Drug on Plasma Metformin Systemic Exposure Coadministered Drug Dose of Coadministered Drug * Dose of Metformin * Geometric Mean Ratio (ratio with/without coadministered drug) No Effect = 1.00 AUC † C max No dosing adjustments required for the following: Glyburide 5 mg 850 mg metformin 0.91 ‡ 0.93 ‡ Furosemide 40 mg 850 mg metformin 1.09 ‡ 1.22 ‡ Nifedipine 10 mg 850 mg metformin 1.16 1.21 Propranolol 40 mg 850 mg metformin 0.90 0.94 Ibuprofen 400 mg 850 mg metformin 1.05 ‡ 1.07 ‡ Cationic drugs eliminated by renal tubular secretion may reduce metformin elimination Cimetidine 400 mg 850 mg metformin 1.40 1.61 Carbonic anhydrase inhibitors may cause metabolic acidosis [ See Warnings and Precautions (5.1) and Drug Interactions (7).] Topiramate 100 mg § 500 mg § metformin 1.25 § 1.07 * All metformin and coadministered drugs were given as single doses † AUC = AUC(INF) ‡ Ratio of arithmetic means § At steady state with topiramate 100 mg every 12 hours and metformin 500 mg every 12 hours; AUC = AUC 0-12h Table 6: Effect of Metformin on Coadministered Drug Systemic Exposure Coadministered Drug Dose of Coadministered Drug * Dose of Metformin * Geometric Mean Ratio (ratio with/without metformin) No Effect = 1.00 AUC † C max No dosing adjustments required for the following: Glyburide
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