Semi-mechanistic population pharmacokinetic model to predict the drug-drug interaction between S-ketamine and ticlopidine in healthy human volunteers.

08:00 EDT 9th August 2018 | BioPortfolio

Summary of "Semi-mechanistic population pharmacokinetic model to predict the drug-drug interaction between S-ketamine and ticlopidine in healthy human volunteers."

Low dose oral S-ketamine is increasingly used in chronic pain therapy, but extensive cytochrome P450 mediated metabolism makes it prone to pharmacokinetic drug-drug interactions. In our study, concentration-time data from five studies was used to develop a semi-mechanistic model that describes the ticlopidine-mediated inhibition of S-ketamine biotransformation. A mechanistic model was implemented to account for reversible and time dependent hepatic CYP2B6 inactivation by ticlopidine, which causes elevated S-ketamine exposure in vivo. A pharmacokinetic model was developed with gut wall and hepatic clearances for S-ketamine, its primary metabolite norketamine and ticlopidine. Nonlinear mixed effects modeling approach was used (NONMEM 7.3.0), and the final model was evaluated with visual predictive checks and sampling-importance-resampling procedure. Our final model produces biologically plausible output and demonstrates that ticlopidine is a strong inhibitor of CYP2B6 mediated S-ketamine metabolism. Simulations from our model may be used to evaluate chronic pain therapy with S-ketamine. This article is protected by copyright. All rights reserved.


Journal Details

This article was published in the following journal.

Name: CPT: pharmacometrics & systems pharmacology
ISSN: 2163-8306


DeepDyve research library

PubMed Articles [29927 Associated PubMed Articles listed on BioPortfolio]

Population pharmacokinetic model of irinotecan and its metabolites in patients with metastatic colorectal cancer.

Irinotecan (CPT-11) is a drug used against a wide range of tumor types. The individualized dosing of CPT-11 is essential to ensure optimal pharmacotherapy in cancer patients, given the wide interindiv...

A Population Pharmacokinetic-pharmacogenetic Model of Lamotrigine in Chinese Children with Epilepsy.

The pharmacokinetics of lamotrigine (LTG) is complex and varies significantly among individuals, especially among children. Therefore, this study aimed to establish a population pharmacokinetic (PPK) ...

Simulations of Valproate Doses Based on an External Evaluation of Pediatric Population Pharmacokinetic Models.

Valproate is an old-generation antiepileptic drug often used in children. The pharmacokinetics of valproate are noteworthy for a large and difficult to predict interindividual variability in measured ...

Use of Population Pharmacokinetic Analyses Among FDA-Approved Biologics.

Biologics, especially monoclonal antibodies, are increasingly important in the pharmaceutical marketplace. Population pharmacokinetic (PK) analyses could be useful to guide the need for dose adjustmen...

Assessing potential drug-drug interactions between dabigatran etexilate and a P-gp inhibitor in renal impairment population using PBPK modeling.

Plasma concentrations of dabigatran (DAB), an active principle of prodrug dabigatran etexilate (DABE), are increased by renal impairment (RI) or co-administration of a P-glycoprotein (P-gp) inhibitor....

Clinical Trials [10973 Associated Clinical Trials listed on BioPortfolio]

Pharmacokinetic Drug-Drug Interaction Study of Rucaparib

The purpose of this study is to assess pharmacokinetic concentrations of multiple probes alone followed by assessment of the same drug pharmacokinetic concentrations when the patient has s...

Validation of Population Pharmacokinetic Model Derived From Healthy Volunteer in Kidney Transplant Recipients

Pharmacokinetic model to predict interaction between tacrolimus and mycophenolate was developed through clinical trial with healthy volunteer. The purpose of this study is to confirm predi...

Basel Stent Kosten Effektivitäts Trial Drug Eluting Balloons vs. Drug Eluting Stents in Small Vessel Interventions

The investigators hypothesize that in a real-world population undergoing percutaneous coronary intervention (PCI) for de-novo stenoses in small native vessels with a diameter

Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction of Evogliptin and Empagliflozin or Dapagliflozin in Healthy Male Adults

A Randomized, Open-label, Multiple-dose, Crossover Study to Investigate the Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction of Evogliptin 5 mg and Empagliflozin 25 mg or Dapaglif...

Phenotypic Drug Probes as Predictors of Drug-drug Interactions With Tacrolimus

Single center, open label crossover study with 2 treatment phases in healthy volunteers. The potential of phenotypic drug probes to predict drug-drug interactions between tacrolimus, vori...

Medical and Biotech [MESH] Definitions

Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.

Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.

A component of the Executive Office of the President established by the Anti-Drug Abuse Act of 1988. The Office establishes policies, priorities, and objectives for national DRUG AND NARCOTIC CONTROL. The goals of the program are to reduce illicit drug use, manufacturing, and trafficking, drug-related crime and violence, and drug-related health consequences.

The action of a drug that may affect the activity, metabolism, or toxicity of another drug.

The action of a drug in promoting or enhancing the effectiveness of another drug.

Quick Search


DeepDyve research library

Relevant Topics

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...

Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Pain Disorder
Pain is a feeling (sharp or dull) triggered in the nervous system which can be transient or constant. Pain can be specific to one area of the body eg back, abdomen or chest or more general all over the body eg muscles ache from the flu. Without pain ...

Searches Linking to this Article