Transfer of insulin lispro across the human placenta: in vitro perfusion studies.
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.


METHODS
Term human placentae from uncomplicated pregnancies were obtained immediately after delivery. Insulin lispro, at concentrations ranging from 100 to 1000 micro U/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 micro U/ml. In contrast, there was a small concentration-dependent transfer to the fetus at concentrations of 580 micro U/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 micro U x min(-1) x g tissue(-1) at maternal levels of 580 micro U/ml and 0.045 micro U x min(-1) x g(-1) tissue at maternal levels of 1000 micro U/ml. Measuring lispro levels in 11 pregnant women revealed that a dose of 50 units may achieve serum concentrations >200 micro U/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.
Boskovic
Rada
R
Division of Clinical Pharmacology and Toxicology, the Hospital for Sick Children, Toronto, Ontario, Canada.
Feig
Denice S
DS
Derewlany
Lidia
L
Knie
Brenda
B
Portnoi
Galina
G
Koren
Gideon
G
D000328:Adult; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D007328:Insulin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D061268:Insulin Lispro; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D010477:Perfusion; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy
D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro