Pharmacokinetics of Metformin during Pregnancy

Abstract

ABSTRACT:Our objective was to evaluate the pharmacokinetics of metformin during pregnancy. Serial blood and urine samples were collected over one steady-state dosing interval in women treated with metformin during early to late pregnancy (n ‫؍‬ 35) and postpartum (n ‫؍‬ 16). Maternal and umbilical cord blood samples were obtained at delivery from 12 women. Metformin concentrations were also determined in breast milk samples obtained over one dosing interval in 6 women. Metformin renal clearance increased significantly in mid (723 ؎ 243 ml/min, P < 0.01) and late pregnancy (625 ؎ 130 ml/min, P < 0.01) compared with postpartum (477 ؎ 132 ml/min). These changes reflected significant increases in creatinine clearance (240 ؎ 70 ml/min, P < 0.01 and 207 ؎ 56 ml/min, P < 0.05 versus 165 ؎ 44 ml/min) and in metformin net secretion clearance (480 ؎ 190 ml/min, P < 0.01 and 419 ؎ 78 ml/min, P < 0.01 versus 313 ؎ 98 ml/min) in mid and late pregnancy versus postpartum, respectively. Metformin concentrations at the time of delivery in umbilical cord plasma ranged between nondetectable (<5 ng/ml) and 1263 ng/ml. The daily infant intake of metformin through breast milk was 0.13 to 0.28 mg, and the relative infant dose was <0.5% of the mother's weight-adjusted dose. Our results indicate that metformin pharmacokinetics are affected by pregnancy-related changes in renal filtration and net tubular transport and can be roughly estimated by the use of creatinine clearance. At the time of delivery, the fetus is exposed to metformin concentrations from negligible to as high as maternal concentrations. In contrast, infant exposure to metformin through the breast milk is low.

Microparticulate and nanoparticulate drug delivery systems for metformin hydrochloride

“…Metformin is distributed into breast milk in small amounts, thus, infant exposure to metformin through the breast milk is low (Sweetman, 2007;Eyal et al, 2010). Metformin readily crosses the placenta and the fetus is exposed to metformin concentrations from negligible to as high as maternal concentrations (Eyal et al, 2010).…”

“…Pregnancy-related changes in renal filtration and net tubular transport affect the pharmacokinetics of metformin, and creatinine clearance may be used roughly for estimation of metformin renal clearance in pregnant patients (Eyal et al, 2010). Metformin is distributed into breast milk in small amounts, thus, infant exposure to metformin through the breast milk is low (Sweetman, 2007;Eyal et al, 2010).…”

Metformin – újabb adatok egy megbízható és hatékony „régi” vércukorcsökkentő készítményről

“…A gyógyszert terhessé-gük alatt szedő várandósokon, terminusban, a köldök-zsinórvérben mérve, méréshatár alattitól (<5 ng/ml) 1263 ng/ml-ig változó vérszintet találtak. Ez utóbbi jó-val alacsonyabb az átlagos anyai plazmakoncentrációnál [22]. Meg kell jegyeznünk, hogy várandósokon az átla-gos plazmakoncentráció alacsonyabb az azonos napi dó-zist szedő nem terhes kortársakban mértnél, aminek oka a metforminclearence terhesség alatti emelkedése [16].…”

Modern Paradigm of the Pregnant-Involving Pharmacological Study: Risk Assessment, Ethical Principles and Regulatory Aspect

“…Moreover, glibenclamide is susceptible to maternal-fetal exchange, therefore, any assessment of alternative dosage regimens exceeding the currently used rang (up to 10 mg BID) must be considered with regard to fetal and neonatal safety [28]. The change in metformin's PK during pregnancy is also associated with transformation of renal filtration and active renal transport [31]. Along with physiological functions, the course of pathophysiological processes also changes during pregnancy.…”