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A Pilot Study of the Maternal-Fetal Pharmacokinetics of Furosemide in Plasma, Urine, and Amniotic Fluid of Hypertensive Parturient Women Under Cesarean Section.
- Source :
-
Journal of clinical pharmacology [J Clin Pharmacol] 2020 Dec; Vol. 60 (12), pp. 1655-1661. Date of Electronic Publication: 2020 Jun 20. - Publication Year :
- 2020
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Abstract
- The third trimester of pregnancy is related to physiological changes that can modify the process of absorption, distribution, metabolism, and excretion and, consequently, the efficacy and toxicity of drugs. However, little is known about furosemide pharmacokinetics and placental transfer in pregnancy. This study evaluated the maternal-fetal pharmacokinetics and distribution to amniotic fluid of furosemide in hypertensive parturient women under cesarean section. Twelve hypertensive parturient women under methyldopa (250 mg/8 h) and/or pindolol (10 mg/12 h) treatment received a 40-mg single oral dose of furosemide 1 to 10 hours before delivery by cesarean section. Blood and urine samples were collected for 12 hours after furosemide administration. At delivery, samples were obtained from maternal and umbilical cord blood (n = 8) to assess the transplacental transfer. Amniotic fluid (n = 4) was collected at the time of delivery. The following furosemide pharmacokinetic parameters were obtained as median (interquartile range): C <subscript>max</subscript> , 403 ng/mL (229 to 715 ng/mL); T <subscript>max</subscript> , 2.00 hours (1.50 to 4.83 hours); elimination half-life (t <subscript>1/2</subscript> ), 2.50 hours (1.77 to 2.97 hours); AUC <subscript>0-12 h</subscript> , 1366 ng⋅h/mL (927 to 2531 ng⋅h/mL); AUC <subscript>0-∞</subscript> , 1580 ng⋅h/mL (1270 to 2881 ng⋅h/mL); CL/F 25.3 L/h (13.8 to 31.4 L/h); CLR, 2.50 L/h (1.77 to 2.97 L/h); CLNR, 22.7 L/h (12.1 to 25.6 L/h); and V <subscript>d</subscript> /F 82.8 L (34.4 to 173 L). The transplacental transfer of furosemide was 0.43 (0.10 to 0.73), and the amniotic fluid concentration was 11.0 ng/mL (5.51 to 14.6 ng/mL). From a clinical point of view, these results suggest that substrates of uridine diphosphate-glucuronosyltransferase isoenzymes such as furosemide may have increased clearance during pregnancy and could require dose adjustment in this population.<br /> (© 2020, The American College of Clinical Pharmacology.)
- Subjects :
- Administration, Oral
Adult
Cesarean Section
Diuretics administration & dosage
Diuretics blood
Diuretics urine
Drug Dosage Calculations
Drug Elimination Routes
Female
Fetal Blood metabolism
Furosemide administration & dosage
Furosemide blood
Furosemide urine
Glucuronosyltransferase metabolism
Humans
Hypertension blood
Hypertension urine
Parturition blood
Parturition urine
Pilot Projects
Pregnancy
Amniotic Fluid metabolism
Diuretics pharmacokinetics
Furosemide pharmacokinetics
Hypertension drug therapy
Hypertension, Pregnancy-Induced
Maternal-Fetal Exchange physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4604
- Volume :
- 60
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 32562572
- Full Text :
- https://doi.org/10.1002/jcph.1681