Publication:
Population pharmacokinetics of mycophenolate mofetil in Thai lupus nephritis patients

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Issued Date

2012

Resource Type

Article

File Type

application/pdf

ISSN

9461965

DOI

10.5414/CP201605

Other identifier(s)

2-s2.0-84861446507

Rights Holder(s)

Scopus

Bibliographic Citation

International Journal of Clinical Pharmacology and Therapeutics. Vol 50, No.4 (2012), p.272-280

Suggested Citation

Punyawudho B., Lertdumrongluk P., Somparn P., Kittanamongkolchai W., Traitanon O., Avihingsanon Y., Vadcharavivad S. Population pharmacokinetics of mycophenolate mofetil in Thai lupus nephritis patients. International Journal of Clinical Pharmacology and Therapeutics. Vol 50, No.4 (2012), p.272-280. doi:10.5414/CP201605 Retrieved from: https://hdl.handle.net/20.500.14740/7092

Title

Population pharmacokinetics of mycophenolate mofetil in Thai lupus nephritis patients

Author(s)

Punyawudho B.
 Lertdumrongluk P.
 Somparn P.
 Kittanamongkolchai W.
 Traitanon O.
 Avihingsanon Y.
 Vadcharavivad S.

Abstract

Objective: Mycophenolic acid (MPA) has become the first-line drug therapy for proliferative lupus nephritis, a common and serious complication of systemic lupus erythematosus. Although a sufficient MPA exposure is required, a high interindividual variability in the pharmacokinetics of MPA has been observed. The knowledge of MPA pharmacokinetics in lupus nephritis patients is limited, especially in Asian patients. This study aimed to develop a population pharmacokinetic model for MPA and determine the population pharmacokinetic parameters and their interindividual variability in Thai patients with lupus nephritis. Methods: A total of 112 MPA plasma concentrations from 14 adult lupus nephritis patients (International Society of Nephrology/Renal Pathology Society Class III/IV) receiving mycophenolate mofetil were included in this study. The data was analyzed using NONMEM. The model evaluation was performed by the bootstrap approach and visual predictive check. Results: A two-compartment model with a lag time best described the data. The estimated mean apparent clearance (CL/F) was 14.5 l/h with an interindividual variability of 45.2%. The estimated mean CL/F was found to be lower than the values previously reported. The estimated mean apparent volume of the central compartment was 12.2 l with an interindividual variability of 166%. None of the covariates were found to significantly influence MPA pharmacokinetics. Conclusion: In this study, a population pharmacokinetic model of MPA in severe lupus nephritis patients was successfully developed. The mean pharmacokinetic parameters were estimated and a high interindividual variability of MPA in this population was observed. This provides evidence to show that individualizing dosage regimens in this population is crucial. The model developed in this study could be used to obtain initial information for MPA dose adjustments in Thai and Asian patients with lupus nephritis. Further studies are required to validate the results and clarify the influence of covariates on MMF pharmacokinetics. ©2012 Dustri-Verlag Dr. K. Feistle.

Subject(s)

Mycophenolic acid 2 morpholinoethyl ester
 Prednisolone
 Drug derivative
 Immunosuppressive agent
 Mycophenolic acid
 Mycophenolic acid 2 morpholinoethyl ester
 Adult
 Article
 Clinical article
 Controlled study
 Disease classification
 Drug absorption
 Drug blood level
 Drug clearance
 Drug distribution
 Drug dose titration
 Female
 Human
 Lupus erythematosus nephritis
 Male
 Population research
 Thailand
 Asian
 Biological model
 Blood
 Ethnology
 Lupus erythematosus nephritis
 Thailand
 Treatment outcome
 Adult
 Asian Continental Ancestry Group
 Female
 Humans
 Immunosuppressive Agents
 Lupus Nephritis
 Male
 Models, Biological
 Mycophenolic Acid
 Thailand
 Treatment Outcome

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URI

https://hdl.handle.net/20.500.14740/7092

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Scopus: Year 1983-2021

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