Rifampin and rifabutin and their metabolism by human liver esterases

C. A. Jamis-Dow, A. G. Katki, J. M. Collins, R. W. Klecker

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

1. The main metabolites of rifampin and rifabutin in man are their respective 25 deacetylated derivatives, but the enzyme(s) responsible for these biotransformations are not known. 2. In experiments with human liver slices and human liver microsomes, the 25 deacetylated derivatives of these drugs were the main metabolites observed. Slices and microsomes metabolized rifabutin 3-6-fold faster than rifampin, in agreement with their relative clearance in patients. Rifabutin partitioned into slices more avidly than rifampin. 3. In microsomal incubations, deacetylation did not require NADPH, but the amount of metabolite at the end of incubation was affected by NADPH. With NADPH the amount of 25 deacetyl rifabutin decreased, whereas the amount of 25 deacetyl rifampin increased slightly. A panel of liver microsomes from seven donors showed a 3-4-fold difference in the formation of 25 deacetyl rifabutin or 25 deacetyl rifampin, with strong correlation between the production of the two metabolites (r2 = 0.94). 4. The production of 25 deacetyl rifabutin and 25 deacetyl rifampin by human liver microsomes was not significantly affected by 1 μM 4 chloromercuricbenzoic acid or bis-(4-nitrophenyl) phosphate, but was completely inhibited by 1 μM paraoxon or 1 μM diisopropylfluorophosphate. These results indicate that in man rifampin and rifabutin are deacetylated to their main metabolites by B-esterases.

Original languageEnglish (US)
Pages (from-to)1015-1024
Number of pages10
JournalXenobiotica
Volume27
Issue number10
DOIs
StatePublished - Oct 30 1997

Fingerprint

Rifabutin
Esterases
Rifampin
Metabolism
Liver
Metabolites
Liver Microsomes
NADP
Paraoxon
Derivatives
Isoflurophate
Carboxylesterase
Biotransformation
Microsomes
Tissue Donors
Acids
Enzymes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

Cite this

Jamis-Dow, C. A., Katki, A. G., Collins, J. M., & Klecker, R. W. (1997). Rifampin and rifabutin and their metabolism by human liver esterases. Xenobiotica, 27(10), 1015-1024. https://doi.org/10.1080/004982597239994
Jamis-Dow, C. A. ; Katki, A. G. ; Collins, J. M. ; Klecker, R. W. / Rifampin and rifabutin and their metabolism by human liver esterases. In: Xenobiotica. 1997 ; Vol. 27, No. 10. pp. 1015-1024.
@article{0ac17fafad44413f8a0c60b9148a273a,
title = "Rifampin and rifabutin and their metabolism by human liver esterases",
abstract = "1. The main metabolites of rifampin and rifabutin in man are their respective 25 deacetylated derivatives, but the enzyme(s) responsible for these biotransformations are not known. 2. In experiments with human liver slices and human liver microsomes, the 25 deacetylated derivatives of these drugs were the main metabolites observed. Slices and microsomes metabolized rifabutin 3-6-fold faster than rifampin, in agreement with their relative clearance in patients. Rifabutin partitioned into slices more avidly than rifampin. 3. In microsomal incubations, deacetylation did not require NADPH, but the amount of metabolite at the end of incubation was affected by NADPH. With NADPH the amount of 25 deacetyl rifabutin decreased, whereas the amount of 25 deacetyl rifampin increased slightly. A panel of liver microsomes from seven donors showed a 3-4-fold difference in the formation of 25 deacetyl rifabutin or 25 deacetyl rifampin, with strong correlation between the production of the two metabolites (r2 = 0.94). 4. The production of 25 deacetyl rifabutin and 25 deacetyl rifampin by human liver microsomes was not significantly affected by 1 μM 4 chloromercuricbenzoic acid or bis-(4-nitrophenyl) phosphate, but was completely inhibited by 1 μM paraoxon or 1 μM diisopropylfluorophosphate. These results indicate that in man rifampin and rifabutin are deacetylated to their main metabolites by B-esterases.",
author = "Jamis-Dow, {C. A.} and Katki, {A. G.} and Collins, {J. M.} and Klecker, {R. W.}",
year = "1997",
month = "10",
day = "30",
doi = "10.1080/004982597239994",
language = "English (US)",
volume = "27",
pages = "1015--1024",
journal = "Xenobiotica",
issn = "0049-8254",
publisher = "Informa Healthcare",
number = "10",

}

Jamis-Dow, CA, Katki, AG, Collins, JM & Klecker, RW 1997, 'Rifampin and rifabutin and their metabolism by human liver esterases', Xenobiotica, vol. 27, no. 10, pp. 1015-1024. https://doi.org/10.1080/004982597239994

Rifampin and rifabutin and their metabolism by human liver esterases. / Jamis-Dow, C. A.; Katki, A. G.; Collins, J. M.; Klecker, R. W.

In: Xenobiotica, Vol. 27, No. 10, 30.10.1997, p. 1015-1024.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Rifampin and rifabutin and their metabolism by human liver esterases

AU - Jamis-Dow, C. A.

AU - Katki, A. G.

AU - Collins, J. M.

AU - Klecker, R. W.

PY - 1997/10/30

Y1 - 1997/10/30

N2 - 1. The main metabolites of rifampin and rifabutin in man are their respective 25 deacetylated derivatives, but the enzyme(s) responsible for these biotransformations are not known. 2. In experiments with human liver slices and human liver microsomes, the 25 deacetylated derivatives of these drugs were the main metabolites observed. Slices and microsomes metabolized rifabutin 3-6-fold faster than rifampin, in agreement with their relative clearance in patients. Rifabutin partitioned into slices more avidly than rifampin. 3. In microsomal incubations, deacetylation did not require NADPH, but the amount of metabolite at the end of incubation was affected by NADPH. With NADPH the amount of 25 deacetyl rifabutin decreased, whereas the amount of 25 deacetyl rifampin increased slightly. A panel of liver microsomes from seven donors showed a 3-4-fold difference in the formation of 25 deacetyl rifabutin or 25 deacetyl rifampin, with strong correlation between the production of the two metabolites (r2 = 0.94). 4. The production of 25 deacetyl rifabutin and 25 deacetyl rifampin by human liver microsomes was not significantly affected by 1 μM 4 chloromercuricbenzoic acid or bis-(4-nitrophenyl) phosphate, but was completely inhibited by 1 μM paraoxon or 1 μM diisopropylfluorophosphate. These results indicate that in man rifampin and rifabutin are deacetylated to their main metabolites by B-esterases.

AB - 1. The main metabolites of rifampin and rifabutin in man are their respective 25 deacetylated derivatives, but the enzyme(s) responsible for these biotransformations are not known. 2. In experiments with human liver slices and human liver microsomes, the 25 deacetylated derivatives of these drugs were the main metabolites observed. Slices and microsomes metabolized rifabutin 3-6-fold faster than rifampin, in agreement with their relative clearance in patients. Rifabutin partitioned into slices more avidly than rifampin. 3. In microsomal incubations, deacetylation did not require NADPH, but the amount of metabolite at the end of incubation was affected by NADPH. With NADPH the amount of 25 deacetyl rifabutin decreased, whereas the amount of 25 deacetyl rifampin increased slightly. A panel of liver microsomes from seven donors showed a 3-4-fold difference in the formation of 25 deacetyl rifabutin or 25 deacetyl rifampin, with strong correlation between the production of the two metabolites (r2 = 0.94). 4. The production of 25 deacetyl rifabutin and 25 deacetyl rifampin by human liver microsomes was not significantly affected by 1 μM 4 chloromercuricbenzoic acid or bis-(4-nitrophenyl) phosphate, but was completely inhibited by 1 μM paraoxon or 1 μM diisopropylfluorophosphate. These results indicate that in man rifampin and rifabutin are deacetylated to their main metabolites by B-esterases.

UR - http://www.scopus.com/inward/record.url?scp=0030764254&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030764254&partnerID=8YFLogxK

U2 - 10.1080/004982597239994

DO - 10.1080/004982597239994

M3 - Article

C2 - 9364739

AN - SCOPUS:0030764254

VL - 27

SP - 1015

EP - 1024

JO - Xenobiotica

JF - Xenobiotica

SN - 0049-8254

IS - 10

ER -

Jamis-Dow CA, Katki AG, Collins JM, Klecker RW. Rifampin and rifabutin and their metabolism by human liver esterases. Xenobiotica. 1997 Oct 30;27(10):1015-1024. https://doi.org/10.1080/004982597239994