Pharmacokinetics (PK) and Modeling of Betamethasone Therapy in Threatened Preterm Birth
| Status: | Recruiting |
|---|---|
| Conditions: | Women's Studies, Women's Studies |
| Therapuetic Areas: | Reproductive |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 11/22/2018 |
| Start Date: | July 2016 |
| End Date: | May 2021 |
| Contact: | David M Haas, MD, MS |
| Email: | dahaas@iu.edu |
| Phone: | 317-880-3949 |
Pharmacokinetics and Modeling of Betamethasone Therapy in Threatened Preterm Birth
Respiratory distress syndrome (RDS) is a life-threatening condition for premature neonates.
Antenatal glucocorticoids have been used clinically in women with threatened preterm birth to
accelerate lung maturation for more than 40 years. The current treatment strategy for women
with threatened preterm delivery is for a standard, "one size fits all" dosing with either
betamethasone (BMZ) or dexamethasone. It is well known that pregnancy introduces additional
variability in response to medication therapy with different physiological changes and
alterations in the activity of drug metabolizing enzymes. The objective of this project is to
evaluate the pharmacokinetic (PK), pharmacodynamic, and pharmacogenetic parameters of
betamethasone (BMZ) and determine the differences in response and benefit in pregnancy. An
individualized dosing approach to medications in pregnancy, such as BMZ, is crucial to
optimize efficacy of this important medication.
Antenatal glucocorticoids have been used clinically in women with threatened preterm birth to
accelerate lung maturation for more than 40 years. The current treatment strategy for women
with threatened preterm delivery is for a standard, "one size fits all" dosing with either
betamethasone (BMZ) or dexamethasone. It is well known that pregnancy introduces additional
variability in response to medication therapy with different physiological changes and
alterations in the activity of drug metabolizing enzymes. The objective of this project is to
evaluate the pharmacokinetic (PK), pharmacodynamic, and pharmacogenetic parameters of
betamethasone (BMZ) and determine the differences in response and benefit in pregnancy. An
individualized dosing approach to medications in pregnancy, such as BMZ, is crucial to
optimize efficacy of this important medication.
After consent, a maternal sample of whole blood will be obtained for DNA isolation.
Investigators will collect plasma samples at 4 time points on all participants. These will be
done at baseline (pre-dose), and 0.5-2 hours, 4-6 hours, and 22-24 hours after the first dose
of BMZ is administered. Investigators will obtain serum for estriol measurement on all
participants before or within 2 hours of antenatal corticosteroid administration and about 24
hours after each dose is given (betamethasone is administered as 2 doses 24 hours apart).
Investigators will obtain a saliva sample for measurement of estriol at the same times.
Participants will be offered optional participation in a more detailed PK portion of the
study. Participants who consent to this part of the study will have additional plasma samples
obtained at a schedule of sampling of approximately 10-15 hours after the first dose and then
6-8 hours, 24, and 48 hours after the 2nd dose. One sample will be collected at each of these
times. At the time of delivery, umbilical cord blood will be collected before being discarded
for DNA, serum and plasma. Four placenta sections will be collected. A maternal blood sample
will also be obtained for serum and plasma. If the investigators are unable to obtain
umbilical cord blood, a buccal swab will be collected from the baby for DNA extraction. A
chart review will be done on the infant within 30 days of birth to review and record neonatal
outcomes.
Investigators will collect plasma samples at 4 time points on all participants. These will be
done at baseline (pre-dose), and 0.5-2 hours, 4-6 hours, and 22-24 hours after the first dose
of BMZ is administered. Investigators will obtain serum for estriol measurement on all
participants before or within 2 hours of antenatal corticosteroid administration and about 24
hours after each dose is given (betamethasone is administered as 2 doses 24 hours apart).
Investigators will obtain a saliva sample for measurement of estriol at the same times.
Participants will be offered optional participation in a more detailed PK portion of the
study. Participants who consent to this part of the study will have additional plasma samples
obtained at a schedule of sampling of approximately 10-15 hours after the first dose and then
6-8 hours, 24, and 48 hours after the 2nd dose. One sample will be collected at each of these
times. At the time of delivery, umbilical cord blood will be collected before being discarded
for DNA, serum and plasma. Four placenta sections will be collected. A maternal blood sample
will also be obtained for serum and plasma. If the investigators are unable to obtain
umbilical cord blood, a buccal swab will be collected from the baby for DNA extraction. A
chart review will be done on the infant within 30 days of birth to review and record neonatal
outcomes.
Inclusion Criteria:
- Gestational age between 23-34 weeks with a diagnosis of threatened preterm labor or
preterm premature rupture of membranes, or other diagnosis with a high likelihood of
preterm delivery where the provider is recommending administering antenatal
corticosteroids
- Singleton gestation
- Live fetus at the time of enrollment
- Being administered antenatal corticosteroids to enhance lung maturity
- Ability to provide written informed consent to participate in the study
Exclusion Criteria:
- Maternal age <18 years old
- Major congenital anomalies
- Known severe abruptio placentae at the time of enrollment
- Multiple gestations
- Hepatic failure (history of hepatic failure, cirrhosis or 2- fold increase in
Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT)
- Renal failure (serum creatinine > 2 mg/dl)
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