K. Jang,1 H. Chung,1 J. Yoon,1 S. Moon,1 S. Yoon,1 K. Kim,2 J. Chung3; 1Department of Clinical Pharmacology and Therapeutics, Seoul, Korea, Republic of, 2Department of Internal Medicine, Seongnam, Korea, Republic of, 3Department of Clinical Pharmacology and Therapeutics, Seongnam, Korea, Republic of
BACKGROUND: Although metformin is widely used in diabetic patients, its pharmacokinetic (PK) and pharmacodynamic (PD) studies have not been conducted in elderly Asian. This study aimed to evaluate the PK and PD of metformin in healthy elderly subjects, and compare those with healthy younger subjects.
METHODS: A total of 12 Korean male subjects aged 65-85 years were enrolled. A single oral dose of metformin at 750 mg was administered 2 hours after having dinner on Day -1 and at 500 mg in the fasting state on Day 1. After 2 hours from the last administration of metformin, 75 g glucose for oral glucose tolerance test (OGTT) was ingested. Serial blood samples for PK were collected up to 12 hours after the last dose. Blood samples for OGTT were taken until 2 hours after glucose ingestion. Tolerability was evaluated throughout the entire study period.
RESULTS: The mean Cmax, AUClast and AUCinf were 1.9, 2.0, and 2.0 times higher for the elderly subjects than the younger subjects, respectively. (p = 0.007, 0.001 and 0.001, respectively). However, Tmax in the elderly subjects was 1.7 hours which was comparable to the result of the young subjects. There was a subtle increase in the average Gmax of 168.8 mg/dL in the elderly subjects compared to the younger subjects (157 mg/dL). Also, the calculated AUGCs (area under the serum glucose concentration -time curve) were slightly higher (the mean AUGC0-2h: 296.3 vs. 260.3 mg*h/dL). No serious adverse events were reported.
CONCLUSION: The systemic exposure to metformin was elevated by 90% or more in elderly subjects than younger subjects, however the blood glucose lowering effect was comparable. The over-exposure of metformin in the elderly might lead to the side effects; therefore, dose adjustment of metformin would be necessary in elderly patients.