Prednisone Pharmacokinetics During Pregnancy and Lactation.

Autor: Ryu RJ; Department of Pharmacy, University of Washington, Seattle, WA, USA., Easterling TR; Department of Pharmacy, University of Washington, Seattle, WA, USA.; Department of Obstetrics & Gynecology, University of Washington, Seattle, WA, USA., Caritis SN; Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA., Venkataramanan R; Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA., Umans JG; MedStar Health Research Institute, and the Georgetown-Howard, Hyattsville, MD, USA.; Universities Center for Clinical and Translational Science, Washington, DC, USA., Ahmed MS; Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA., Clark S; Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA., Kantrowitz-Gordon I; Department of Family and Child Nursing, University of Washington, Seattle, WA, USA., Hays K; Department of Pharmacy, University of Washington, Seattle, WA, USA., Bennett B; Department of Pharmacy, University of Washington, Seattle, WA, USA., Honaker MT; Department of Pharmaceutics, University of Washington, Seattle, WA, USA., Thummel KE; Department of Pharmaceutics, University of Washington, Seattle, WA, USA., Shen DD; Department of Pharmacy, University of Washington, Seattle, WA, USA.; Department of Pharmaceutics, University of Washington, Seattle, WA, USA., Hebert MF; Department of Pharmacy, University of Washington, Seattle, WA, USA.; Department of Obstetrics & Gynecology, University of Washington, Seattle, WA, USA.
Jazyk: angličtina
Zdroj: Journal of clinical pharmacology [J Clin Pharmacol] 2018 Sep; Vol. 58 (9), pp. 1223-1232. Date of Electronic Publication: 2018 May 07.
DOI: 10.1002/jcph.1122
Abstrakt: To evaluate the steady-state pharmacokinetics of prednisone and its metabolite prednisolone in pregnant and lactating female subjects, 19 subjects received prednisone (4-40 mg/day orally) in early (n = 3), mid (n = 9), and late (n = 13) pregnancy as well as postpartum with (n = 2) and without (n = 5) lactation. Serial blood and urine samples were collected over 1 dosing interval. Prednisone and its metabolite, prednisolone, steady-state noncompartmental pharmacokinetic parameters were estimated. During pregnancy, prednisone apparent oral clearance increased with dose (35.1 ± 11.4 L/h with 5 mg, 52.6 ± 5.2 L/h with 10 mg, and 64.3 ± 6.9 L/h with 20 mg, P = .001). Similarly, unbound prednisone apparent oral clearance increased with dose. In addition, prednisolone renal clearance increased with dose (0.3 ± 0.3 L/h with 5 mg, 0.5 ± 0.4 L/h with 10 mg, and 1.3 ± 1.1 L/h with 20 mg, P = .002). Higher prednisone (r = 0.57, P ≤ .05) and prednisolone (r = 0.75, P ≤ .05) concentrations led to a higher percentage of unbound drug. Breast-milk/plasma area under the concentration-time curve ratios were 0.5-0.6 for prednisone and 0.02-0.03 for prednisolone. Relative infant doses were 0.35% to 0.53% and 0.09% to 0.18%, for prednisone and prednisolone, respectively. Prednisone and prednisolone exhibit dose- and concentration-dependent pharmacokinetics during pregnancy, and infant exposure to these agents via breast milk is minimal.
(© 2018, The American College of Clinical Pharmacology.)
Databáze: MEDLINE
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