TY - JOUR
T1 - Dose-independent pharmacokinetics of metformin in rats
T2 - Hepatic and gastrointestinal first-pass effects
AU - Choi, Young H.
AU - Kim, Sang G.
AU - Lee, Myung G.
PY - 2006/11
Y1 - 2006/11
N2 - Pharmacokinetic parameters of metformin were evaluated after intravenous and oral administration (50,100, and 200 mg/kg) in rats. The hepatic, gastric, and intestinal first-pass effects were also measured after intravenous, intraportal, intragastric, and intraduodenal administration (100 mg/kg) in rats. The total area under the plasma concentration-time curve from time zero to time infinity (AUC) values were dose-proportional after both intravenous and oral dose ranges studied. After oral administration (100 mg/kg), approximately 4.39% of oral dose was not absorbed and extent of absolute oral bioavailability (F) value was approximately 29.9%. The gastrointestinal first-pass effect of metformin was approximately 53.8% of oral dose in rats (the gastric and intestinal first-pass effects were approximately 23.1 and 30.7%, respectively), and the hepatic first-pass effect was approximately 27.1% after absorption into the portal vein. Since approximately 41.8% of oral metformin was absorbed into the portal vein, the value of 27.1% is equivalent to 11.3% of oral dose. The first-pass effects of metformin in the lung and heart were almost negligible in rats. The low F value of metformin in rats was mainly due to considerable gastrointestinal first-pass effects. The stability of metformin, distribution of metformin between plasma and blood cells, and factors affecting protein binding of metformin to 4% human serum albumin were also discussed.
AB - Pharmacokinetic parameters of metformin were evaluated after intravenous and oral administration (50,100, and 200 mg/kg) in rats. The hepatic, gastric, and intestinal first-pass effects were also measured after intravenous, intraportal, intragastric, and intraduodenal administration (100 mg/kg) in rats. The total area under the plasma concentration-time curve from time zero to time infinity (AUC) values were dose-proportional after both intravenous and oral dose ranges studied. After oral administration (100 mg/kg), approximately 4.39% of oral dose was not absorbed and extent of absolute oral bioavailability (F) value was approximately 29.9%. The gastrointestinal first-pass effect of metformin was approximately 53.8% of oral dose in rats (the gastric and intestinal first-pass effects were approximately 23.1 and 30.7%, respectively), and the hepatic first-pass effect was approximately 27.1% after absorption into the portal vein. Since approximately 41.8% of oral metformin was absorbed into the portal vein, the value of 27.1% is equivalent to 11.3% of oral dose. The first-pass effects of metformin in the lung and heart were almost negligible in rats. The low F value of metformin in rats was mainly due to considerable gastrointestinal first-pass effects. The stability of metformin, distribution of metformin between plasma and blood cells, and factors affecting protein binding of metformin to 4% human serum albumin were also discussed.
KW - Gastrointestinal and hepatic first-pass effects
KW - Metformin
KW - Pharmacokinetics
KW - Rats
UR - http://www.scopus.com/inward/record.url?scp=33750053217&partnerID=8YFLogxK
U2 - 10.1002/jps.20744
DO - 10.1002/jps.20744
M3 - Article
C2 - 16937336
AN - SCOPUS:33750053217
SN - 0022-3549
VL - 95
SP - 2543
EP - 2552
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 11
ER -