Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome

The use of metformin throughout gestation by pregnant women with polycystic ovary syndrome (PCOS) significantly reduces the number of first trimester spontaneous abortions and the rate of occurrence of gestational diabetes. The objective of this study was to investigate the pharmacokinetics and the placental transfer of metformin in pregnant women with PCOS. Eight pregnant women with PCOS taking 850 mg metformin every 12 h during the third trimester of pregnancy were evaluated. Maternal blood samples were collected at steady state during the dose interval (0-12 h). Maternal and umbilical cord blood samples were also obtained at delivery. Metformin plasma concentrations were analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using a non-compartmental model. Data are reported as median and minimum and maximum values. Metformin pharmacokinetic parameters were: t(A1/2), 3.8 (2.8-5.4) h; t(max), 2.0 (0.5-3.0) h; C(max), 1.4 (0.5-2.1) mg/L; C(mean), 0.5 (0.2-0.9) mg/L; AUC(0-12), 6.4 (1.1-9.2) mg h/L; Cl/f, 105 (60-274) L/h; Vd/f, 551 (385-1173) L; median fluctuation, 89 (79-95)%. Umbilical/maternal metformin plasma concentration ratios were 0.7 (0.4-1.3). Metformin oral clearance (Cl/f) had increased in our patients relative to nonpregnant healthy volunteers or diabetic patients. Therefore, lower plasma metformin concentrations were observed for nondiabetic pregnant women with PCOS. Future studies should be conducted to demonstrate the therapeutic efficacy of metformin during pregnancy. Caution is warranted as umbilical/maternal metformin plasma concentrations ratios of around 0.7 require metformin dosage adjustment.

Women during Aldermaston Peace march 1965

Women with placards and banners during Aldermaston Peace march 1965. The march covered the distance between Ipswich and Brisbane, Australia, walked in relays covering approximately two miles each. Most relay sections were sponsored by one or more individual organisations.

Women during Aldermaston Peace March, Brisbane Australia 1964

Marchers with placards and aprons during Aldermaston Peace March, April 5 1964, Brisbane Australia. The march covered the distance between Ipswich and Brisbane, Australia. Marchers walked in relays covering approximately two miles each. Most relay sections were sponsored by one or more individual organisations.

Women and children during Aldermaston Peace march 1965

Women and children with placards and banners during Aldermaston Peace march 1965. The march covered the distance between Ipswich and Brisbane, Australia, walked in relays covering approximately two miles each. Most relay sections were sponsored by one or more individual organisations.

Women wearing peace aprons during Peace march in Brisbane, Australia 1963

Women wearing peace aprons during Peace march in Brisbane, Australia 1963. Cars can be seen in the background.

Women and men during the 1963 Peace March, Brisbane, Australia

Women and men during Peace march in Brisbane, Australia 1963. Car can be seen in the background. Two men one with drum follow the women, one of which has a banner Women strike for peace say U.A.W. The Union of Australian Women is a national organisation that was formed in 1950. Its aim is to work for the status and wellbeing of women across the world. It has been involved in a wide variety of campaigns that concern women. The Union of Australian Women networks with other women's community and union groups on such issues.

Women with umbrellas during Peace march on Sunday April 5th 1964, Brisbane.

Two women with umbrellas outside a cemetery during Peace march, Sunday April 5th Brisbane, Australia, 1964.

Members of the Union of Australian Women with banner during Hiroshima Day 1964, Brisbane

Members of the Union of Australian Women with banner during Hiroshima Day 1964, Brisbane, Australia. The Union of Australian Women is a national organisation that was formed in 1950. Its aim is to work for the status and wellbeing of women across the world. It has been involved in a wide variety of campaigns that concern women. The Union of Australian Women networks with other women's community and union groups on such issues.