Recent lessons learned from population pharmacokinetic studies of mycophenolic acid: physiological, genomic, and drug interactions leading to the prediction of drug effects

2022 ◽  
Author(s):  
Yan Rong ◽  
Vrunda Patel ◽  
Tony K.L. Kiang
Keyword(s):  
Drug Interactions ◽  
Mycophenolic Acid ◽  
Drug Effects ◽  
Lessons Learned ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Studies

scholarly journals Hierarchy of evidence in interpretation of clinical significance of drug interactions

2012 ◽  
Vol 65 (1-2) ◽  
pp. 45-49
Author(s):  
Bozana Nikolic ◽  
Miroslav Savic
Keyword(s):  
Drug Metabolism ◽  
Drug Interactions ◽  
Clinical Significance ◽  
Health Professionals ◽  
Molecular Entity ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Studies ◽  
Potential Interactions

Introduction. Since drug interactions may result in serious adverse effects or failure of therapy, it is of huge importance that health professionals base their decisions about drug prescription, dispensing and administration on reliable research evidence, taking into account the hierarchy of data sources for evaluation. Clinical Significance of Potential Interactions - Information Sources. The sources of data regarding drug interactions are numerous, beginning with various drug reference books. However, they are far from uniformity in the way of choosing and presenting putative clinically relevant interactions. Clinical Significance of Potential Interactions - Interpretation of Information. The difficulties in interpretation of drug interactions are illustrated through the analysis of a published example involving assessment made by two different groups of health professionals. Systematic Evaluation of Drug-Drug Interaction. The potential for interactions is mainly investigated before marketing a drug. Generally, the in vitro, followed by in vivo studies are to be performed. The major metabolic pathways involved in the metabolism of a new molecular entity, as well as the potential of induction of human enzymes involved in drug metabolism are to be examined. In the field of interaction research it is possible to make use of the population pharmacokinetic studies as well as of the pharmacodynamic assessment, and also the postregistration monitoring of the reported adverse reactions and other literature data. Conclusion. In vitro and in vivo drug metabolism and transport studies should be conducted to elucidate the mechanisms and potential for drug-drug interactions. The assessment of their clinical significance should be based on well-defined and validated exposure-response data.

Interaction between Traditional Chinese Medicine and Anticoagulant/Antiplatelet Drugs

2019 ◽  
Vol 20 (9) ◽  
pp. 701-713 ◽  
Author(s):  
Jiajia Li ◽  
Qing Liang ◽  
GuangChun Sun
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Drug Interactions ◽  
Adverse Reactions ◽  
Bleeding Risk ◽  
Antiplatelet Drugs ◽  
Pharmacokinetic Studies ◽  
Drug Databases ◽  
Concurrent Use ◽  
Anticoagulant Drugs

Background: Traditional Chinese medicine (TCM) has been used for medical purposes since the ancient time and has gradually gained recognition worldwide. Nowadays, patients with thrombus presiding to anticoagulant/ antiplatelet drugs prefer taking TCM. However, an increasing number of studies on herb–drug interactions have been shown. Nevertheless, findings are frequently conflicting and vague. In this review, we discuss the herb–drug interactions between TCM and anticoagulant/antiplatelet drugs to provide guidance on concomitant ingestion with anticoagulant/antiplatelet drugs. Methods: We undertook a structured search of medicine and drug databases for peer-reviewed literature using focused review questions. Results: Danshen, Ginkgo, Ginger, H. Perforatum, SMY and Puerarin injection had directional regulation effects on the efficacy of anticoagulant drugs by altering the CYPs, pharmacokinetic indexs and hemorheological parameters. H. Perforatum inhibited the efficacy of Clopidogrel by enhancing the CYP3A4 activity and Ginkgo increased the efficacy of Ticlopidine. Additionally, Renshen, the formulae except SMY and injections except Puerarin injection could increase or decrease the efficacy of anticoagulant/antiplatelet drugs via regulating the CYPs, platelet aggregation, hemorheological parameters and others. Conclusion: Some cases have reported that TCMs may increase the bleeding risk or has no effect on coagulation when anticoagulant/antiplatelet drugs are concurrently used. However, pharmacokinetic studies have presented either consistent or slightly varying results. So it is difficult to ascertain whether the concurrent use of TCM may increase or reduce the pharmacologic effects of anticoagulant/antiplatelet drugs with adverse reactions. Therefore, herb–drug interactions of TCM and anticoagulant/antiplatelet drugs should be further explored and defined.

Tacrolimus pharmacokinetic drug interactions: effect of prednisone, mycophenolic acid or sirolimus

2009 ◽  
Vol 23 (1) ◽  
pp. 137-145 ◽  
Author(s):  
Sung-In Park ◽  
Claudia R. Felipe ◽  
Paula G. Pinheiro-Machado ◽  
Riberto Garcia ◽  
Fernanda B. Fernandes ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Mycophenolic Acid ◽  
Pharmacokinetic Drug

Population pharmacokinetics of mycophenolic acid in Mexican patients with lupus nephritis

Lupus ◽  
2020 ◽  
Vol 29 (9) ◽  
pp. 1067-1077
Author(s):  
Melissa Romano-Aguilar ◽  
Juan Eduardo Reséndiz-Galván ◽  
Susanna Edith Medellín-Garibay ◽  
Rosa del Carmen Milán-Segovia ◽  
Marco Ulises Martínez-Martínez ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Mycophenolic Acid ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Immunosuppressive Drug ◽  
Stochastic Simulations ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Variability ◽  
Clinical Genetic ◽  
Post Dose

Background Mycophenolic acid (MPA) is an effective oral immunosuppressive drug used to treat lupus nephritis (LN), which exhibits large pharmacokinetic variability. This study aimed to characterize MPA pharmacokinetic behaviour in Mexican LN patients and to develop a population pharmacokinetic model which identified factors that influence MPA pharmacokinetic variability. Methods Blood samples from LN patients treated with mycophenolate mofetil (MMF) were collected pre dose and up to six hours post dose. MPA concentrations were determined by a validated ultra-performance liquid chromatography tandem mass spectrometry technique. Patients were genotyped for polymorphisms in enzymes (UGT1A8, 1A9 and 2B7) and transporters (ABCC2 and SLCO1B3). The anthropometric, clinical, genetic and co-medication characteristics of each patient were considered as potential covariates to explain the variability. Results A total of 294 MPA concentrations from 40 LN patients were included in the development of the model. The data were analysed using NONMEM software and were best described by a two-compartment linear model. MPA CL, Vc, Vp, Ka and Q were 15.4 L/h, 22.86 L, 768 L, 1.28 h−1 and 20.3 L/h, respectively. Creatinine clearance and prednisone co-administration proved to have influence on clearance, while body weight influenced Vc. The model was internally validated, proving to be stable. MMF dosing guidelines were obtained through stochastic simulations performed with the final model. Conclusions This is the first MPA population pharmacokinetic model to have found that co-administration of prednisone results in a considerable increase on clearance. Therefore, this and the other covariates should be taken into account when prescribing MMF in order to optimize the immunosuppressant therapy in patients with LN.

Sign in / Sign up

Export Citation Format

Share Document