Altered methylprednisolone pharmacodynamics in healthy subjects with Histamine N-Methyltransferase C314T genetic polymorphism

Yi Hon Yuen, William J. Jusko, Vicky Elizabeth Spratlin, Michael W. Jann

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

This study investigated the potential differences in methylprednisolone pharmacodynainics between healthy subjects with different histamine N-methyltransferase (HNMT) C314T genotypes. Six individuals with C/C genotype and 4 with C/T genotype were administered a single intravenous dose of methylprednisolone 0.6 mg/kg ideal body weight in a randomized 2-period manner. Methylprednisolone plasma concentrations were fitted with a 1-compartment model. Cortisol and whole blood histamine suppression were assessed by indirect response models, with circadian baseline cortisol analyzed by Fourier analysis. The area between the baseline and effect curve and the area under the effect versus time curve suppression ratio were used to characterize plasma histamine suppression. Methylprednisolone pharmacokinetics and plasma and whole blood histamine suppression were similar between the 2 genotype groups. Median nadir of cortisol and the 50% inhibitory concentration for cortisol were significantly higher in subjects with C/T genotype than those with C/C genotype (P = .031 and .033, respectively, Wilcoxon rank sum test). Subjects who are heterozygous for the T314 variant allele thus appeared less sensitive to the suppressive effects of methylprednisolone on cortisol secretion.

Original languageEnglish (US)
Pages (from-to)408-417
Number of pages10
JournalJournal of Clinical Pharmacology
Volume46
Issue number4
DOIs
StatePublished - Apr 1 2006

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Histamine N-Methyltransferase
Methylprednisolone
Genetic Polymorphisms
Healthy Volunteers
Genotype
Hydrocortisone
Histamine
Nonparametric Statistics
Ideal Body Weight
Fourier Analysis
Inhibitory Concentration 50
Area Under Curve
Pharmacokinetics
Alleles

Keywords

  • Corticosteroids
  • Cortisol suppression
  • HNMT polymorphism
  • Histamine suppression
  • Methylprednisolone pharmacodynamics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Altered methylprednisolone pharmacodynamics in healthy subjects with Histamine N-Methyltransferase C314T genetic polymorphism. / Yuen, Yi Hon; Jusko, William J.; Spratlin, Vicky Elizabeth; Jann, Michael W.

In: Journal of Clinical Pharmacology, Vol. 46, No. 4, 01.04.2006, p. 408-417.

Research output: Contribution to journalArticle

Yuen, Yi Hon ; Jusko, William J. ; Spratlin, Vicky Elizabeth ; Jann, Michael W. / Altered methylprednisolone pharmacodynamics in healthy subjects with Histamine N-Methyltransferase C314T genetic polymorphism. In: Journal of Clinical Pharmacology. 2006 ; Vol. 46, No. 4. pp. 408-417.
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