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.

Keywords: breast milk; pharmacokinetics; prednisolone; prednisone; pregnancy.

Figure 1.

A) Correlation between prednisone concentrations and prednisone percent unbound during pregnancy (diamonds; early, mid-, and late pregnancy) receiving oral prednisone doses from 3.5 to 40 mg and ≥ 12 weeks postpartum (squares; with and without lactation) receiving doses from 2 to 20 mg. B) Correlation between prednisolone concentrations and prednisolone percent unbound during pregnancy (diamonds; early-, mid-, and late-pregnancy) receiving oral prednisone doses from 3.5 to 40 mg and ≥ 12 weeks postpartum (squares; with and without lactation) receiving doses from 2 to 20 mg.

Figure 2.

A representative subject’s unbound steady-state plasma concentration-time profiles during mid-pregnancy and 12 weeks postpartum receiving prednisone 10 mg once daily.

Figure 3.

A representative concentration and time curve of prednisone and prednisolone in plasma and breast milk of a subject receiving prednisone 15 mg orally every 24 hours at 12 weeks postpartum.