Pharmacokinetics of betamethasone in twin and singleton pregnancy

Objective: The aims of the study were to compare the pharmacokinetics of betamethasone in singleton pregnancy with the pharmacokinetics in twin pregnancy and to assess the adrenal suppression produced by betamethasone. Study Design: We measured serial betamethasone and cortisol levels in 30 singleton and 21 twin pregnancies after the first dose of betamethasone and calculated the pharmacokinetic parameters for betamethasone including volume of distribution, half-life, and clearance. We also measured cord and maternal blood levels of betamethasone at the birth of infants of 13 singleton and 9 twin pregnancies. Results: The half-life of betamethasone in mothers with twin pregnancies was significantly shorter than that in mothers with singleton pregnancies (7.2 ± 2.4 versus 9.0 ± 2.7 hours; P < .017). Clearance of betamethasone in the twin pregnancies appeared greater than in singleton pregnancies (8.4 ± 6.4 versus 5.7 ± 3.1 L/h; P = .06) but did not reach statistical significance. Volume of distribution was similar in the two groups. Because the time between the last dose of betamethasone and birth varied widely (range, 2-158 hours), mothers with a longer interval after treatment tended to have a higher cord-to-maternal betamethasone ratio than did mothers with a shorter interval in both twin and singleton pregnancies. This finding indicated delayed fetal clearance, but the correlation was weak (R² = 0.29 for twins and 0.08 for singletons). Conclusion: The shorter half-life of betamethasone in twin pregnancy than in singleton pregnancy may cause the level of betamethasone to be subtherapeutic for lung maturation in twin pregnancy.