Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Induction of CYP2E1 activity in liver transplant patients as measured by chlorzoxazone 6-hydroxylation

Burckart, GJ and Frye, RF and Kelly, P and Branch, RA and Jain, A and Fung, JJ and Starzl, TE and Venkataramanan, R (1998) Induction of CYP2E1 activity in liver transplant patients as measured by chlorzoxazone 6-hydroxylation. Clinical Pharmacology and Therapeutics, 63 (3). 296 - 302. ISSN 0009-9236

[img]
Preview
PDF
Accepted Version
Available under License : See the attached license file.

Download (1MB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)

Abstract

Objective: To examine the phenotypic expression of CYP2E1 in liver transplant patients, as measured by the in vivo probe chlorzoxazone, and to evaluate CYP2E1 activity over me after transplantation. Methods: Thirty-three stable liver transplant: patients were given 250 mg chlorzoxazone within 1 year after transplantation as part of a multiprobe CYP cocktail; urine and blood were collected for 8 hours. Chlorzoxazone and 6-hydroxychlorzoxazone concentrations were determined by HPLC. Twenty-eight healthy control subjects, eight patients with moderate to severe liver disease, and four patients who had not received liver transplants were also studied for comparison. The chlorzoxazone metabolic ratio, calculated as the plasma concentration of 6-hydroxychlorzoxazone/chlorzoxazone at 4 hours after chlorzoxazone administration, was used as the phenotypic, index. In a subgroup of patients and control subjects, additional blood samples were obtained to allow for the calculation of chlorzoxazone pharmacokinetic parameters by noncompartmental methods. Results: The chlorzoxazone metabolic ratio for the liver transplant patients in the first month after transplantation (mean ± SD, 6.4 ± 5.1) was significantlp higher than that after 1 month after surgery (2.1 ± 2.0), when the chlorzoxazone metabolic ratio was not different from control subjects (0.8 ± 0.5). The chlorzoxazone metabolic ratios in the patients who had not received liver transplants (1.1 ± 0.7) were equivalent to those of healthy control subjects. The maximum observed 6-hydroxychlorzoxazone plasma concentration was 3046 ± 1848 ng/ml in seven liver transplant patients in the first month after surgery compared with 1618 ± 320 ng/ml in 16 healthy control subjects (p < 0.05). The maximum observed concentration of chlorzoxazone, the chlorzoxazone apparent oral clearance, and the formation clearance of 6-hydroxychlorzoxazone were also significantly different between the groups. Conclusions: We conclude that significant induction of CYP2E1, as indicated by the chlorzoxazone metabolic, ratio, occurs in the first month after surgery in liver transplant patients and that drugs that are substrates for CYP2E1 may require dosage alteration during that period. Contrary to expectations, drug metabolism is not uniformly depressed after liver transplantation.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Burckart, GJ
Frye, RF
Kelly, P
Branch, RArab13@pitt.eduRAB13
Jain, A
Fung, JJ
Starzl, TEtes11@pitt.eduTES11
Venkataramanan, Rrv@pitt.eduRV
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 March 1998
Date Type: Publication
Journal or Publication Title: Clinical Pharmacology and Therapeutics
Volume: 63
Number: 3
Page Range: 296 - 302
DOI or Unique Handle: 10.1016/s0009-9236(98)90161-8
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0009-9236
Other ID: uls-drl:31735062127299, Starzl CV No. 2008
Date Deposited: 08 Apr 2010 17:34
Last Modified: 13 Oct 2017 22:55
URI: http://d-scholarship.pitt.edu/id/eprint/5394

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com


Actions (login required)

View Item View Item