As compounds are optimized for greater potency during pharmaceutical discovery, their aqueous solubility often decreases, making them less viable as orally-administered drugs.
The potency-insolubility conundrum in pharmaceuticals: Mechanism and solution for hepatitis C protease inhibitors
As compounds are optimized for greater potency during pharmaceutical discovery, their aqueous solubility often decreases, making them less viable as orally-administered drugs.
Relationships between the antidotal efficacy and structure, PK/PD parameters and bio-relevant molecular descriptors of AChE reactivating oximes: inclusion and integration to biopharmaceutical classification systems
The therapeutic outcome of oximes used as reactivators of phosphorylated human acetylcholinesterase (AChE) is influenced, among other factors, by their biological distribution, their in vivo ability...
In vitro-in vivo correlations: general concepts, methodologies and regulatory applications
The major objective of in vitro-in vivo correlations is to be able to use in vitro data to predict in vivo performance serving as a surrogate for an in vivo bioavailability test and to support biowaivers.
Chromatographic lipophilicity as a predictor of antiproliferative activity of 17-picolyl and 17-picolinylidene androstane derivatives toward prostate cancer
Lipophilicity is a molecular parameter widely used in estimation of biological and environmental behavior of many substances (1-3).
Nonclinical and pharmacokinetic assessments to evaluate the potential of tedizolid and linezolid to affect mitochondrial function
Prolonged treatment with the oxazolidinone linezolid is associated with myelosuppression, lactic acidosis, and neuropathies, toxicities likely caused by impairment of mitochondrial protein synthesis (MPS). To evaluate the potential of the novel oxazolidinone tedizolid...
Predicting drug-drug interactions involving multiple mechanisms using physiologically based pharmacokinetic modeling: A case study with ruxolitinib
Physiologically based pharmacokinetic modeling was applied to characterize the potential drug–drug interactions for ruxolitinib.
MITOsym®: A Mechanistic, Mathematical Model of Hepatocellular Respiration and Bioenergetics
MITOsym, a new mathematical model of hepatocellular respiration and bioenergetics, has been developed in partnership with the DILIsym® model with the purpose of translating in vitro compound screening data...
Eslicarbazepine Acetate Monotherapy: A Population Ppharmacokinetic Analysis
Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED), approved by the US Food and Drug Administration for the treatment of partial-onset seizures (POS) as monotherapy or…
Relationship between exposure and efficacy of eslicarbazepine acetate monotherapy
Eslicarbazepine acetate (ESL) is a once-daily, oral antiepileptic drug (AED), approved by the US Food and Drug Administration for the treatment of partialonset seizures (POS) as monotherapy or adjunctive...
Relationship Between Eslicarbazepine Exposure and Efficacy of Eslicarbazepine Acetate Adjunctive Therapy
Eslicarbazepine acetate (ESL; Aptiom®) is a novel once-daily (QD) oral antiepileptic drug, approved in then US, Canada and the EU as adjunctive treatment of partial-onset seizures (POS). ESL is extensively...
Relationship Between Eslicarbazepine Exposure and Safety Endpoints for Eslicarbazepine Acetate Adjunctive Therapy
Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED), approved in the US, Canada and the EU as adjunctive treatment of partial-onset seizures (POS). After oral administration, ESL...
Relationship Between Eslicarbazepine Exposure and Safety Endpoints for Eslicarbazepine Acetate Monotherapy
In two Phase III trials (093-045 and -046) of eslicarbazepine acetate (ESL) monotherapy in patients with partial-onset seizures (POS) uncontrolled by 1−2 antiepileptic drugs (AEDs), the incidence of...
Simulations Plus Reports First Quarter FY2015 Preliminary Revenues
Preliminary revenues increase 50% to first quarter record $3.96 million
Predicting pharmacokinetics of anti-cancer drug, famitinib in human using physiologically based pharmacokinetic model
This study is to establish physiologically based pharmacokinetic (PBPK) models of famitinib in rat and monkey, and then to predict the pharmacokinetics and tissue distribution of famitinib in human based on the PBPK models.
Computational classification models for predicting the interaction of drugs with P-glycoprotein and breast cancer resistance protein
P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) are two members of the adenosine triphosphate (ATP) binding cassette (ABC) family of transporters which...
Novel Orally Swallowable IntelliCap(®) Device to Quantify Regional Drug Absorption in Human GI Tract Using Diltiazem as Model Drug
Typically, colonic absorption of a drug is mandatory for a sustained release formulation to hold the drug's plasma level for more than 12 or 24 h above the minimum therapeutic plasma concentration (efficacy).
Improvement of trospium-specific absorption models for fasted and fed states in humans
The purpose of this study was to mechanistically interpret the oral absorption pattern of trospium in fasted and fed states by means of gastrointestinal simulation technology.
Best of Both Worlds: Combining Pharma Data and State of the Art Modeling Technology to Improve in silico pKa Prediction
In a unique collaboration between a software company and a pharmaceutical company, we were able to develop a new in silico pKa prediction tool with outstanding prediction quality.