Uptake and distribution of lidocaine in fetal lambs.
The fetal uptake of lidocaine was measured continually and quantitatively during and after a constant rate intravenous (iv) maternal infusion into five chronically prepared pregnant ewes. Lidocaine, 6 mg/kg (base), was infused at a constant rate for 1 h and measurements continued to 5 h. Rate of fetal uptake was determined from the product of the umbilical venous (UV) and fetal aortic (FA) concentration difference and umbilical blood flow (Qu). Total fetal uptake was determined by integrating fetal uptake rate with respect to time. Maternal and fetal protein binding was determined, and its effect on fetal blood concentrations was evaluated. Mean total fetal uptake as it related to time and infused dose increased linearly (r = 0.998, P less than 0.001) with a constant, weight-normalized fetal-maternal dose fraction of 0.45 during the infusion. Despite rapidly declining blood concentrations after the infusion, uptake increased an additional 17%. The sevenfold variation in uptake appeared to be inversely related to the biodegradation rate of lidocaine. Fetal-maternal concentration ratios (F/M) increased during declining blood concentrations. Protein binding determinations for maternal and fetal blood were 43.6 +/- 2.48% and 26.9 +/- 1.59%, respectively. These values were used to calculate the F/M in conjunction with the maternal and fetal pH. At maternal-fetal equilibrium the calculated F/M, 1.0 +/- 0.05, closely approximated the observed, 1.0 +/- 0.03. Variations in lidocaine concentrations among the vital organs 4 h after the infusion were small, but high concentrations of metabolites were found in the lungs and kidneys. The results challenge the validity of placental transfer estimates commonly based on the F/M and umbilical cord blood concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Kennedy
R L
RL
Department of Anesthesiology, West Virginia University, Morgantown.
Bell
J U
JU
Miller
R P
RP
Doshi
D
D
de Sousa
H
H
Kennedy
M J
MJ
Heald
D L
DL
Bettinger
R
R
David
Y
Y
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007262:Infusions, Intravenous; D008012:Lidocaine / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011485:Protein Binding; D012756:Sheep; D014018:Tissue Distribution
D001798:Blood Proteins; D008012:Lidocaine