Transfer of Insulin Lispro Across the Human Placenta
In vitro perfusion studies
- Rada Boskovic, MD1,
- Denice S. Feig, MD2,
- Lidia Derewlany, PHD1,
- Brenda Knie, RT1,
- Galina Portnoi, MD1 and
- Gideon Koren, MD1
- 1Division of Clinical Pharmacology and Toxicology, the Hospital for Sick Children, Toronto, Ontario, Canada
- 2Department of Endocrinology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
OBJECTIVE—Insulin lispro (Humalog), a human insulin analog, has a more rapid onset, earlier peak, and shorter duration of glucose lowering activity than regular human insulin. However, it is not known whether insulin lispro crosses the human placenta and reaches the fetus. Therefore, the objective of the present study was to examine whether insulin lispro crosses the placenta using the technique of perfusing a human placental lobule in vitro.
RESEARCH DESIGN AND METHODS—Term human placentae from uncomplicated pregnancies were obtained immediately after delivery. Insulin lispro, at concentrations ranging from 100 to 1000 μU/ml, was introduced into the maternal reservoir. The maternal side of the placenta was perfused with constant concentration of lispro insulin; the fetal circulation was closed. Samples were drawn from both the maternal and fetal circulations at regular intervals. The appearance of insulin lispro in the fetal circulation was analyzed by a specific radioimmunoassay.
RESULTS—No placental transfer of lispro could be detected during perfusion with 100 and 200 μU/ml. In contrast, there was a small concentration-dependent transfer to the fetus at concentrations of 580 μU/ml and higher, detectable after at least an hour of constant concentration of insulin lispro during perfusion. The rate of placental transfer was 0.019 μU · min−1 · g tissue−1 at maternal levels of 580 μU/ml and 0.045 μU · min−1 · g−1 tissue at maternal levels of 1000 μU/ml. Measuring lispro levels in 11 pregnant women revealed that a dose of 50 units may achieve serum concentrations >200 μU/ml with apparent linear correlation between dose and levels.
CONCLUSIONS—Insulin lispro is not likely to cross the placenta at a single standard dose. This study suggests that insulin lispro is unlikely to reach or harm the unborn baby.
Address correspondence and reprint requests to Gideon Koren, MD, FACMT, FRCPC, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada. E-mail:.
Received for publication 7 October 2002 and accepted in revised form 10 February 2003.
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