Document Detail


Pharmacokinetics of oral mycophenolate mofetil in volunteer subjects with varying degrees of hepatic oxidative impairment.
MedLine Citation:
PMID:  8728347     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Eighteen patients with compensated alcoholic cirrhosis participated in a single-dose pharmacokinetic study of oral mycophenolate mofetil (MMF). Participants were divided into groups of 6 patients each with mild, moderate, or severe hepatic oxidative impairment as defined by the aminopyrine breath test (APBT). Clinically, hepatic disease was of mild or moderate severity. Six healthy volunteers were included as control subjects. Plasma and urine samples were collected over 96 hours and assayed for the active metabolite mycophenolic aced (MPA) and the glucuronide conjugate, MPAG. Plasma protein binding of MPA also was determined in 6 unrelated patients with cirrhosis. Cirrhosis did not grossly affect plasma pharmacokinetics or plasma binding of MPA. Maximum plasma concentrations (C(max)) and area under the curve (AUC) of MPA and MPAG consistently decreased, increased, and then decreased as oxidative impairment declined from normal to severe. Patients with cirrhosis had comparable or greater recovery of administered drug substance in urine than controls, showing that cirrhosis did not affect the extent of MMF absorption. Urine clearance of MPAG was two times higher in the group with severe impairment than in the other groups. Creatinine clearance was similar in all groups. These results suggest progressive impairment of hepatic glucuronidation of MPA and induction of renal glucuronidation in patients with severe hepatic oxidative impairment.
Authors:
G Parker; R Bullingham; B Kamm; M Hale
Related Documents :
12666917 - Human donor liver and serum concentrations of perfluorooctanesulfonate and other perflu...
12745047 - Methanol ingestion: prevention of toxic sequelae after massive ingestion.
6718457 - Lack of acute alcohol effects on estradiol and luteinizing hormone in female macaque mo...
3710427 - Serum hyaluronate in liver diseases: study by enzymoimmunological assay.
17267027 - Lh pulsatile release patterns, follicular growth and function during repetitive periods...
9216697 - Elevated levels of serum and plasma metalloproteinases in patients with gastric cancer.
Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  36     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  1996 Apr 
Date Detail:
Created Date:  1996-09-30     Completed Date:  1996-09-30     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  332-44     Citation Subset:  IM    
Affiliation:
Roche Global Development, Palo Alto, California 94303, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Adult
Humans
Immunosuppressive Agents / administration & dosage,  blood,  pharmacokinetics*,  urine
Liver Cirrhosis / drug therapy
Male
Middle Aged
Mycophenolic Acid / administration & dosage,  analogs & derivatives*,  blood,  pharmacokinetics,  urine
Prospective Studies
Proteins / metabolism
Chemical
Reg. No./Substance:
0/Immunosuppressive Agents; 0/Proteins; 24280-93-1/Mycophenolic Acid; 9242ECW6R0/mycophenolate mofetil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Effect of time of administration on the pharmacokinetics and tolerance of doxazosin in healthy male ...
Next Document:  Grapefruit juice alters the systemic bioavailability and cardiac repolarization of terfenadine in po...