Effects of rifampin on cyclosporine disposition in kidney recipients with tuberculosis

J. H. Shon, Y. R. Yoon, K. A. Kim, Ji-Young Park, I. J. Cha, Y. W. Kim, Y. H. Kim, J. G. Shin

Research output: Contribution to journalArticle

Abstract

Background: We present a case whose plasma cyclosporine concentrations were markedly decreased after adding antituberculosis medications. To assess the effect of rifampin on this pharmacokinetic interaction, we evaluated the pharmacokinetic changes of cyclosporine in kidney-transplanted patients with tuberculosis before and after withdrawing rifampin. Methods: Two separate full pharmacokinetic studies of cyclosporine were performed in four kidney recipients with tuberculosis before and one month after withdrawing rifampin from antituberculosis medications. Multiple blood samples were repeatedly drawn after morning oral dose of cyclosporine, and cyclosporine concentrations were determined by HPLC method. Pharmacokinetic parameters were estimated from noncompartmental method using WinNonlin®. Results: After withdrawing rifampin, changing patterns of all pharmacokinetic parameters were consistent in all 4 subjects. Corrected Cmax and AUC estimated on the same 100mg dose basis were significantly increased from 291.1 ± 54.1 ng/ml to 950.7±174.7 ng/ml and from 1483.1±92.0 ng/ml · h to 6047.2 ± 666.6 ng /ml ± hr, respectively (p<0.01). Total oral clearance (Cl/F) estimated during administration of rifampin(19.8 ± 3.5 L/kg) was decreased to 6.0 ± 0.9 L/kg after withdrawing rifampin. However, the prolongation of half-life was not statistically significant (6.1 ± 1.7 hour vs 10.6 ± 1.1 hour). Conclusions: These results strongly suggest that rifampin markedly decrease the plasma concentration of cyclosporine coadministered through pharmacokinetic interaction, and careful dose readjustment should be considered from frequent monitoring of plasma cyclosporine concentrations in patients taking both cyclosporine and antituberculosis medications including rifampin.

Original languageEnglish
Pages (from-to)91-100
Number of pages10
JournalJournal of Korean Society for Clinical Pharmacology and Therapeutics
Volume8
Issue number1
Publication statusPublished - 2000 Jan 1
Externally publishedYes

Fingerprint

Rifampin
Cyclosporine
Tuberculosis
Kidney
Pharmacokinetics
Life Support Care
Area Under Curve
Half-Life
High Pressure Liquid Chromatography

Keywords

  • Cyclosporine
  • Drug interaction
  • Pharmacokinetics
  • Rifampin
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Effects of rifampin on cyclosporine disposition in kidney recipients with tuberculosis. / Shon, J. H.; Yoon, Y. R.; Kim, K. A.; Park, Ji-Young; Cha, I. J.; Kim, Y. W.; Kim, Y. H.; Shin, J. G.

In: Journal of Korean Society for Clinical Pharmacology and Therapeutics, Vol. 8, No. 1, 01.01.2000, p. 91-100.

Research output: Contribution to journalArticle

Shon, J. H. ; Yoon, Y. R. ; Kim, K. A. ; Park, Ji-Young ; Cha, I. J. ; Kim, Y. W. ; Kim, Y. H. ; Shin, J. G. / Effects of rifampin on cyclosporine disposition in kidney recipients with tuberculosis. In: Journal of Korean Society for Clinical Pharmacology and Therapeutics. 2000 ; Vol. 8, No. 1. pp. 91-100.
@article{2fd6f1b6aa05469890d5d8764ea730dc,
title = "Effects of rifampin on cyclosporine disposition in kidney recipients with tuberculosis",
abstract = "Background: We present a case whose plasma cyclosporine concentrations were markedly decreased after adding antituberculosis medications. To assess the effect of rifampin on this pharmacokinetic interaction, we evaluated the pharmacokinetic changes of cyclosporine in kidney-transplanted patients with tuberculosis before and after withdrawing rifampin. Methods: Two separate full pharmacokinetic studies of cyclosporine were performed in four kidney recipients with tuberculosis before and one month after withdrawing rifampin from antituberculosis medications. Multiple blood samples were repeatedly drawn after morning oral dose of cyclosporine, and cyclosporine concentrations were determined by HPLC method. Pharmacokinetic parameters were estimated from noncompartmental method using WinNonlin{\circledR}. Results: After withdrawing rifampin, changing patterns of all pharmacokinetic parameters were consistent in all 4 subjects. Corrected Cmax and AUC estimated on the same 100mg dose basis were significantly increased from 291.1 ± 54.1 ng/ml to 950.7±174.7 ng/ml and from 1483.1±92.0 ng/ml · h to 6047.2 ± 666.6 ng /ml ± hr, respectively (p<0.01). Total oral clearance (Cl/F) estimated during administration of rifampin(19.8 ± 3.5 L/kg) was decreased to 6.0 ± 0.9 L/kg after withdrawing rifampin. However, the prolongation of half-life was not statistically significant (6.1 ± 1.7 hour vs 10.6 ± 1.1 hour). Conclusions: These results strongly suggest that rifampin markedly decrease the plasma concentration of cyclosporine coadministered through pharmacokinetic interaction, and careful dose readjustment should be considered from frequent monitoring of plasma cyclosporine concentrations in patients taking both cyclosporine and antituberculosis medications including rifampin.",
keywords = "Cyclosporine, Drug interaction, Pharmacokinetics, Rifampin, Therapeutic drug monitoring",
author = "Shon, {J. H.} and Yoon, {Y. R.} and Kim, {K. A.} and Ji-Young Park and Cha, {I. J.} and Kim, {Y. W.} and Kim, {Y. H.} and Shin, {J. G.}",
year = "2000",
month = "1",
day = "1",
language = "English",
volume = "8",
pages = "91--100",
journal = "Journal of Korean Society for Clinical Pharmacology and Therapeutics",
issn = "1225-5467",
publisher = "Korean Society Clinical Pharmacology and Therapeutics",
number = "1",

}

TY - JOUR

T1 - Effects of rifampin on cyclosporine disposition in kidney recipients with tuberculosis

AU - Shon, J. H.

AU - Yoon, Y. R.

AU - Kim, K. A.

AU - Park, Ji-Young

AU - Cha, I. J.

AU - Kim, Y. W.

AU - Kim, Y. H.

AU - Shin, J. G.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Background: We present a case whose plasma cyclosporine concentrations were markedly decreased after adding antituberculosis medications. To assess the effect of rifampin on this pharmacokinetic interaction, we evaluated the pharmacokinetic changes of cyclosporine in kidney-transplanted patients with tuberculosis before and after withdrawing rifampin. Methods: Two separate full pharmacokinetic studies of cyclosporine were performed in four kidney recipients with tuberculosis before and one month after withdrawing rifampin from antituberculosis medications. Multiple blood samples were repeatedly drawn after morning oral dose of cyclosporine, and cyclosporine concentrations were determined by HPLC method. Pharmacokinetic parameters were estimated from noncompartmental method using WinNonlin®. Results: After withdrawing rifampin, changing patterns of all pharmacokinetic parameters were consistent in all 4 subjects. Corrected Cmax and AUC estimated on the same 100mg dose basis were significantly increased from 291.1 ± 54.1 ng/ml to 950.7±174.7 ng/ml and from 1483.1±92.0 ng/ml · h to 6047.2 ± 666.6 ng /ml ± hr, respectively (p<0.01). Total oral clearance (Cl/F) estimated during administration of rifampin(19.8 ± 3.5 L/kg) was decreased to 6.0 ± 0.9 L/kg after withdrawing rifampin. However, the prolongation of half-life was not statistically significant (6.1 ± 1.7 hour vs 10.6 ± 1.1 hour). Conclusions: These results strongly suggest that rifampin markedly decrease the plasma concentration of cyclosporine coadministered through pharmacokinetic interaction, and careful dose readjustment should be considered from frequent monitoring of plasma cyclosporine concentrations in patients taking both cyclosporine and antituberculosis medications including rifampin.

AB - Background: We present a case whose plasma cyclosporine concentrations were markedly decreased after adding antituberculosis medications. To assess the effect of rifampin on this pharmacokinetic interaction, we evaluated the pharmacokinetic changes of cyclosporine in kidney-transplanted patients with tuberculosis before and after withdrawing rifampin. Methods: Two separate full pharmacokinetic studies of cyclosporine were performed in four kidney recipients with tuberculosis before and one month after withdrawing rifampin from antituberculosis medications. Multiple blood samples were repeatedly drawn after morning oral dose of cyclosporine, and cyclosporine concentrations were determined by HPLC method. Pharmacokinetic parameters were estimated from noncompartmental method using WinNonlin®. Results: After withdrawing rifampin, changing patterns of all pharmacokinetic parameters were consistent in all 4 subjects. Corrected Cmax and AUC estimated on the same 100mg dose basis were significantly increased from 291.1 ± 54.1 ng/ml to 950.7±174.7 ng/ml and from 1483.1±92.0 ng/ml · h to 6047.2 ± 666.6 ng /ml ± hr, respectively (p<0.01). Total oral clearance (Cl/F) estimated during administration of rifampin(19.8 ± 3.5 L/kg) was decreased to 6.0 ± 0.9 L/kg after withdrawing rifampin. However, the prolongation of half-life was not statistically significant (6.1 ± 1.7 hour vs 10.6 ± 1.1 hour). Conclusions: These results strongly suggest that rifampin markedly decrease the plasma concentration of cyclosporine coadministered through pharmacokinetic interaction, and careful dose readjustment should be considered from frequent monitoring of plasma cyclosporine concentrations in patients taking both cyclosporine and antituberculosis medications including rifampin.

KW - Cyclosporine

KW - Drug interaction

KW - Pharmacokinetics

KW - Rifampin

KW - Therapeutic drug monitoring

UR - http://www.scopus.com/inward/record.url?scp=0033695259&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033695259&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0033695259

VL - 8

SP - 91

EP - 100

JO - Journal of Korean Society for Clinical Pharmacology and Therapeutics

JF - Journal of Korean Society for Clinical Pharmacology and Therapeutics

SN - 1225-5467

IS - 1

ER -