Prednisone Pharmacokinetics During Pregnancy and Lactation

Rachel J. Ryu, Thomas R. Easterling, Steve N. Caritis, Raman Venkataramanan, Jason G. Umans, Mahmoud Ahmed, Shannon Clark, Ira Kantrowitz-Gordon, Karen Hays, Brooke Bennett, Matthew T. Honaker, Kenneth E. Thummel, Danny D. Shen, Mary F. Hebert

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
JournalJournal of Clinical Pharmacology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Prednisone
Lactation
Prednisolone
Pharmacokinetics
Pregnancy
Human Milk
Postpartum Period
Urine
Kidney
Pharmaceutical Preparations

Keywords

  • Breast milk
  • Pharmacokinetics
  • Prednisolone
  • Prednisone
  • Pregnancy

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Ryu, R. J., Easterling, T. R., Caritis, S. N., Venkataramanan, R., Umans, J. G., Ahmed, M., ... Hebert, M. F. (Accepted/In press). Prednisone Pharmacokinetics During Pregnancy and Lactation. Journal of Clinical Pharmacology. https://doi.org/10.1002/jcph.1122

Prednisone Pharmacokinetics During Pregnancy and Lactation. / Ryu, Rachel J.; Easterling, Thomas R.; Caritis, Steve N.; Venkataramanan, Raman; Umans, Jason G.; Ahmed, Mahmoud; Clark, Shannon; Kantrowitz-Gordon, Ira; Hays, Karen; Bennett, Brooke; Honaker, Matthew T.; Thummel, Kenneth E.; Shen, Danny D.; Hebert, Mary F.

In: Journal of Clinical Pharmacology, 01.01.2018.

Research output: Contribution to journalArticle

Ryu, RJ, Easterling, TR, Caritis, SN, Venkataramanan, R, Umans, JG, Ahmed, M, Clark, S, Kantrowitz-Gordon, I, Hays, K, Bennett, B, Honaker, MT, Thummel, KE, Shen, DD & Hebert, MF 2018, 'Prednisone Pharmacokinetics During Pregnancy and Lactation' Journal of Clinical Pharmacology. https://doi.org/10.1002/jcph.1122
Ryu, Rachel J. ; Easterling, Thomas R. ; Caritis, Steve N. ; Venkataramanan, Raman ; Umans, Jason G. ; Ahmed, Mahmoud ; Clark, Shannon ; Kantrowitz-Gordon, Ira ; Hays, Karen ; Bennett, Brooke ; Honaker, Matthew T. ; Thummel, Kenneth E. ; Shen, Danny D. ; Hebert, Mary F. / Prednisone Pharmacokinetics During Pregnancy and Lactation. In: Journal of Clinical Pharmacology. 2018.
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