Aims: No study has evaluated the BET pharmacokinetics in twin
pregnancies separated by chorionicity. The aim this study is to describe
and compare the BET pharmacokinetic parameters in singleton, dichorionic
(DC) and monochorionic (MC) twin pregnancies in the third trimester of
pregnancy. Methods: Twenty-six pregnant women received an intramuscular
dose of 6 mg of BET sodium phosphate plus 6 mg BET acetate. Serial blood
samples were collected for 24 hours after the first intramuscular BET
esters dose. BET plasma concentrations were quantified using a validated
HPLC analytical method. BET pharmacokinetic parameters were obtained
employing a non-compartment model, and were compared using ANOVA’s test
with Tukey’s multiple comparisons test. Correlations between clinical
features and pharmacokinetic parameters were analyzed using Pearson’s
correlation. Preliminary data on the BET placental transfer were also
presented. Results: The geometric mean (IC 95%) of AUC0-∞ 670.0
(504.3-805.2) vs 434.9 (311.2-539.6) ng.h/mL and the CL/F 18.38
(13.84-22.65) vs 29.40 (21.17-36.69) were significantly lower and
higher, respectively, in DC twin pregnancies compared to singleton.
Others pharmacokinetic parameters did not differ among the groups.
Conclusions: Data from this study suggest that the presence of two
fetoplacental units may increase the BET metabolism by CYP3A4 enzyme and
increase its elimination. Pharmacokinetic-pharmacodynamic clinical
studies are needed to investigate whether this BET pharmacokinetic
changes have clinical repercussions for the newborns and require dose
adjustment in DC twin pregnancies.