Prednisone Pharmacokinetics During Pregnancy and Lactation

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.

The Effect of Pregnancy and Inflammatory Bowel Disease on the Pharmacokinetics of Drugs Related to Inflammatory Bowel Disease—A Systematic Literature Review

“…For corticosteroids, no studies were found for pregnant women with IBD. However, from the literature search, five articles concerning betamethasone (BET) and two articles covering prednisone and prednisolone were found for other indications than IBD [28][29][30][31][32][33][34]. However, in the clinical setting, sometimes dosing advice needs to be determined for drugs (e.g., corticosteroids) that are not investigated in pregnant women with IBD.…”

“…All studies mentioned that the clearance of BET increased during pregnancy. This is likely to be originating from the CYP3A4 enzyme and 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) activities [32][33][34]. Prednisone and prednisolone are affected by these enzymes, too.…”

Parenthood With Kidney Failure: Answering Questions Patients Ask About Pregnancy

“…Tacrolimus, prednisolone, and azathioprine all have minimal transfer into the breast milk. [124][125][126][127] Quinapril, enalapril, and captopril are suitable for lactating mothers requiring resumption of renin-angiotensin blockade. 128…”

Impact of Changes in Free Concentrations and Drug-Protein Binding on Drug Dosing Regimens in Special Populations and Disease States

“…However, for pharmacokinetic reasons such as an absence of change in the apparent oral clearance of free prednisolone, dose adjustment of prednisone may not be required during prenatal period. 28 In a study by Soldin, O.P., 29 the author demonstrated, using tandem mass spectrometry, a rise in free thyroxine (FT4) serum concentrations very early in pregnancy followed by a decrease in FT4 during the remaining of the pregnancy. These two parameters are important because they mirror the physiology of FT4 in gestation.…”