Metformin serum concentrations during pregnancy and post partum - A clinical study in patients with polycystic ovary syndrome.

BACKGROUND AND OBJECTIVES: Metformin is used to treat gestational diabetes. It is also used to treat women with polycystic ovary syndrome and has been shown to prevent late miscarriage and preterm birth. However, increased renal clearance during pregnancy causes a decline in serum concentrations of metformin. The aim of this study was to explore the time course of the pregnancy-related changes in metformin pharmacokinetics and the return to the non-pregnant state. METHOD: A subgroup of women in the PregMet2 study (n = 73) agreed to provide serum samples at three time-points in pregnancy (gestational weeks 19, 28 and 32) and once in post partum, (either 2, 4 or 8 weeks after delivery). Serum metformin concentrations were compared using a four-parameter logistic model. FINDINGS: The mean steady-state serum concentration of metformin during pregnancy was 9.39 µmoL/L, whereas the post partum concentration was 12.36 µmoL/L, an increase of 32% (p = 0,019). This change took place already during the first 2 weeks post partum. CONCLUSION: Clinicians who treat pregnant women with metformin should be aware of the significant decrease in metformin concentration mediated by pregnancy, and the rapid increase after delivery, as it may impact both the therapeutic efficacy and the risk of adverse drug reactions.

[Dosing of digitoxin in clinical practice]. / Dosering av digitoksin i klinisk praksis.

BACKGROUND: In 2007, new Norwegian guidelines suggested that serum concentrations of digitoxin should be in the interval 8 - 15 nmol/l, which is about 50 % lower than previous recommendations. MATERIAL AND METHODS: We studied trends in dosing and serum concentrations of digitoxin in the period 2000 - 08, based on 13 054 serum samples sent to our laboratory for analysis in that period. RESULTS: The median serum concentration of digitoxin was stable until the end of 2006 (at about 25 nmol/l); then it gradually decreased from 2007 until the end of 2008 (to 19 nmol/l). The mean daily dose decreased from 66 microg to 56 microg in the study period. At a given dose, patients above 85 years of age had serum concentrations that were almost twice as high as those for patients younger than 55 years. This age effect was particularly pronounced from 65 years. INTERPRETATION: Serum concentrations of digitoxin have gradually decreased after 2007, but are often higher than the new reference range. To obtain serum concentrations within the new reference interval, doses at least as low as those currently recommended should be used, particularly in the oldest patients.