In vitro ADME provides a set of parameters that predict how a drug will behave in the human body. BioMaxLab conducts custom drug absorption, distribution, metabolism research that can assess drug permeability, metabolic stability and clearance, drug-drug interaction, metabolite identification, CYP and UGT phenotyping and identification, CYP and UGT induction and/or inhibition, and protein binding. levitra kamagra, kamagra superactive, cialis viagra, acheter lioresal ligne

Absorption Study (CaCo-2):

Our absorption study model is designed to classify the absorption potential of our customers' compounds. We use Caco-2 cell monolayers to predict intestinal drug absorption. We routinely run assays for our customers that determine active and passive transport of a compound across cell monolayers.

Distribution Study: Cell permeability and efflux assays (MDR1-MDCKII):

The P-gp transporter is an efflux transporter that is encoded by the ABCB1 gene. P-gp is also known as P-glycoprotein and the Multi-Drug Resistance transporter 1 (MDR1). P-gp (MDR1) is expressed in many tissues of the body including in the kidney on the apical side of the intestinal lumen, the apical side of the bile canaliculus in liver hepatocytes, the apical membrane of proximal tubule epithelial cells and the apical side of the capillaries in the blood brain barrier (BBB). P-gp (MDR1) serves to limit the absorption of substrates, protect them from entering the brain and also to mediate their renal and hepatic elimination.

Human P-gp (MDR1) is known to be a determinant of drug absorption, distribution, and excretion of a number of clinically important drugs. P-gp is widely expressed in major organs, and, more specifically, P-gp is highly expressed in the capillaries of the blood brain barrier (BBB) and poses a barrier to brain penetration of its substrates. Given that P-gp efflux liability can be a major hurdle for CNS therapeutic drugs to cross the BBB and reach the target, the interactions of CNS compounds with P-gp may lead to the lack of CNS activity as a result of the decreased brain penetration. Thus, the prediction and understanding of the relevance of P-gp-mediated efflux transport have become important activities in the discovery and development of CNS drugs. Transwell-based assays using polarized MDCKII and MDR1-MDCKII cell lines provide a great tool to classify compounds as P-gp substrates. Comparison of the efflux ratios between MDR1-MDCKII and MDCKII transwell assays can provide a measure of the specific human P-gp-mediated efflux activity.

  • Apical vs. Basolateral permeability (Caco-2, pH 6.5/7.4)
  • Apical vs. Basolateral permeability (Caco-2, pH 7.4/7.4)
  • Apical vs. Basolateral permeability (Caco-2, pH 7.4/7.4 + verapamil)
  • Apical vs. Basolateral permeability (MDCKII, pH 7.4/7.4)
  • Apical vs. Basolateral permeability (MDR1-MDCKII, pH 7.4/7.4)
  • Apical vs. Basolateral permeability (MDR1-MDCKII, pH 7.4/7.4 + verapamil)
  • Basolateral vs. Apical permeability (Caco-2, pH 6.5/7.4)
  • Basolateral vs. Apical permeability (Caco-2, pH 7.4/7.4)
  • Basolateral vs. Apical permeability (Caco-2, pH 7.4/7.4 + verapamil)
  • Basolateral vs. Apical permeability (MDCKII, pH 7.4/7.4)
  • Basolateral vs. Apical permeability (MDR1-MDCKII, pH 7.4/7.4)
  • Basolateral vs. Apical permeability (MDR1-MDCKII, pH 7.4/7.4 + verapamil)
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BioMaxLab is expertise in performing studies on drug metabolic stability and clearance. While metabolic stability is helpful when trying to determine the potential half-life of a compound, the intrinsic clearance of drug candidates can help to confirm whether metabolism is the main clearance pathway when it is compared with the total body clearance in vivo. Our in vitro ADME metabolic stability and intrinsic clearance assays are conducted in liver microsomes, liver S9, cryopreserved hepatocytes from human, Cynomolgus monkey, Beagle dog, Sprague-Dawley rat, and CD-1 mouse. We also determine metabolic stability when a compound is dosed to animals DRUG METABOLISM & PHARMACOKINETICS. The time points are customized for each project, and the deliverables include raw data, percent remaining, and half-life values. priser cialis, Comprar Genericoo Viagra (Sildenafil) en Linea, Beste Online Apotheke Generic Viagra
BioMaxLab is able to identify, generate, and compare metabolite profiles to assist with species selection for toxicology studies. We will use the state-of-the-art mass spectrometry to analyze samples from in vitro metabolic stability assays or in vivo dosing studies. We search the data sets for potential metabolites, and compare the time profiles of parent compound loss and metabolite formation using enzyme sources from various animal species. Metabolite identification and profiling studies can also be specifically designed to look for unique or disproportionate human metabolites. We determine possible major metabolites using HPLC-UV detection and identify major metabolites using LC-MSn and NMR methods. farmacias online kamagra, vendita viagra su internet, come comprare viagra senza ricetta medica, comprare levitra on line
CYP and UGT phenotyping, or identification, determines the CYP and/or UGT enzymes that are involved in the metabolism of a compound. BioMaxLab will use FDA-approved criteria in this study including specific chemical inhibition, and/or recombinant enzymes. We also perform correlation analysis that involves a donor bank of liver microsomes of at least 10 donors. Pilot studies will be conducted to determine the appropriate reaction conditions for each project. custom writing services, writing an essay, how to write a personal essay

Drug-drug interactions involves inhibition and/or induction of drug metabolizing enzymes. Inhibition of drug metabolizing enzymes is a major mechanism of drug-drug interactions. The majority of these enzymes are CYPs.

CYP Inhibition Studies

These studies are conducted with HLM or recombinant enzymes, FDA-accepted probe substrates, and control inhibitors. Both IC50 and Ki values can be determined, and the pre-incubation of the test article with microsomes and NADPH are used to assess time-dependent inhibition. Alternatively, we can use recombinant CYP450 enzymes with fluorogenic probe substrates in screening assays.

UGT Inhibition Studies

Recombinant UGT enzymes are used to assess the IC50 values of a test article with respect to the most common isoforms.

CYP Induction Studies

Enzyme induction following drug administration can lead to enhanced clearance of co-medications or itself, causing a drug-drug interaction, therapeutic failure, patient management, and potentially other safety issues. Cryopreserved human hepatocytes from one or more donors are used to assess the potential of a compound to induce the activity of a drug metabolizing CYP. In addition to directly studying enzyme activity, we are also able to determine CYP mRNA or protein expression induction using RT-PCR or Western Analysis, respectively (two FDA-accepted validation methods) upon request by the clients.

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Drug efficacy and disposition are influenced by binding of a drug to plasma proteins, primarily human serum albumin, or α1-acid glycoprotein. High drug-protein binding can both reduce the fraction of free drug available for target sites and prolong the duration of drug activity. BioMaxLab will use equilibrium dialysis , ultrafiltration using Thermo rapid equilibrium dialysis (RED) device and HTDialysis 96-well micro-equilibrium dialysis device. Multiple concentrations can be tested to obtain Kd estimates. We can also use in vivo samples to assess binding values. viagra naturale farmacia senza ricetta, priligy acquisto on line, vendita kamagra italia, priligy acquisto on line
Cytotoxicity is a critical area of concern for drug candidates. Hepatocyte cytotoxicity is a major cause of drug candidate failure, both pre- and post-market launch. BioMaxLab will conduct cytotoxicity assays for testing the potential of drug candidate-induced cytotoxicity both in liver cell lines, such as Hep G2 or Hep 3B, or using human or rat hepatocytes. We will use XTT as well as LDH assays.
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