Citation: Journal of Clinical Pharmacology. 2018 May 07.Journal: Journal of clinical pharmacology.Published: 2018ISSN: 0091-2700.Full author list: Ryu RJ; Easterling TR; Caritis SN; Venkataramanan R; Umans JG; Ahmed MS; Clark S; Kantrowitz-Gordon I; Hays K; Bennett B; Honaker MT; Thummel KE; Shen DD; Hebert MF.UI/PMID: 29733485.Subject(s): IN PROCESS -- NOT YET INDEXEDInstitution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Journal ArticleDigital Object Identifier: https://dx.doi.org/10.1002/jcph.1122 (Click here)Abbreviated citation: J Clin Pharmacol. 2018 May 07.Local Holdings: Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2006.Abstract: 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.Abstract: Copyright (c) 2018, The American College of Clinical Pharmacology.