Abstract
The objective of this study was to determine the pharmacokinetic parameters of clonidine during pregnancy compared with previously published data in nonpregnant subjects. Serial blood and urine samples were collected in 17 women during mid to late pregnancy over one steady-state dosing interval to determine clonidine noncompartmental pharmacokinetic parameters (n = 17) and creatinine clearance. In six of these pregnant subjects, maternal and umbilical cord (venous and arterial) plasma samples were collected at the time of delivery for measurement of clonidine concentrations. Clonidine apparent oral clearance was found to be 440 ± 168 ml/min during pregnancy compared with 245 ± 72 ml/min as previously reported in nonpregnant subjects (p < 0.0001) (Cunningham et al., 1994). There was a strong correlation (r = 0.82, p < 0.001) between clonidine renal clearance, adjusted for variation in glomerular filtration rate, and urine pH. Umbilical cord to maternal plasma clonidine concentration ratios were 1.0 ± 0.1 (arterial) and 1.0 ± 0.1 (venous). In conclusion, clonidine is cleared more rapidly in pregnant women than in nonpregnant subjects. At the time of delivery, the fetus is exposed to similar plasma clonidine concentrations as the mother.
Footnotes
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This work was supported in part by the National Institutes of Health National Institute of Child Health and Human Development [Grant 5U10-HD047892] (Unit Network Obstetric-Fetal Pharmacology Research); the National Institutes of Health National Center for Research Resources [Grants T32-RR023256, M01-RR00037, RR023256]; and the University of Washington Multidisciplinary Predoctoral Research Training Program.
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Parts of this work were previously presented as a poster at the following conference: Buchanan ML, Easterling TR, Carr DB, Pon V, Shen DD, and Hebert MF (2007) Clonidine in pregnancy: an OPRU network study. American College of Clinical Pharmacy Annual Conference. 2007 Oct 14–17; Denver, CO. American College of Clinical Pharmacy, Lenexa, KS.
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.108.024984.
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ABBREVIATIONS: LC/MS, liquid chromatography/mass spectrometry; AUCτ, area under the plasma concentration-time curve over one dosing interval; CL/F, apparent oral clearance; CLrenal, renal clearance; Ae,τ, amount of clonidine excreted unchanged in the urine over one dosing interval; GFR, glomerular filtration rate; CrCl, creatinine clearance; fu, fraction unbound in plasma.
- Received October 6, 2008.
- Accepted December 29, 2008.
- U.S. Government work not protected by U.S. copyright.
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