scholarly journals In Situ Intestinal Perfusion of Irinotecan: Application to P-gp Mediated Drug Interaction and Introduction of an Improved HPLC Assay

2011 ◽  
Vol 14 (2) ◽  
pp. 138 ◽  
Author(s):  
Abdullah Khalil Rabba ◽  
Luqin Si ◽  
Kewen Xue ◽  
Ming Li ◽  
Gao Li
Keyword(s):  
Intestinal Permeability ◽  
Internal Standard ◽  
Parent Drug ◽  
Reversed Phase ◽  
Intestinal Perfusion ◽  
Control Group ◽  
Intestinal Toxicity ◽  
In Situ Intestinal Perfusion

PURPOSE: To determine experimentally the intestinal permeability of the anticancer prodrug irinotecan, and to quantify the amount of its cytotoxic metabolite SN-38 that is intestinally excreted (exsorped) as a predictor of intestinal toxicity, and to assess the effect of p-glycoprotein (p-gp) inhibitors (verapamil as a model) on the permeability and toxicity of irinotecan. METHODS: Single pass intestinal perfusion of rat’s whole length small intestines is applied to assess the permeability of the parent drug and quantify the intestinally excreted metabolite. The perfusion solution contained 30μg/ml of irinotecan (control group) without or with verapamil (verapamil group). A simple reversed phase HPLC method with UV detection is developed and validated for simultaneous determination of irinotecan and SN-38 using camptothecin as an internal standard. RESULTS: HPLC-UV method found to be simple, specific, accurate, and precise. Effective permeability coefficient of irinotecan found to be 4.9±1.7 10-3 mm/min and was doubled in verapamil group (P=0.007). Average cumulative amount of SN-38 exsorped found to be 29 ng/cm over 2 hours perfusion time which was decreased to 15 ng/cm in verapamil group (P=0.016). CONCLUSIONS: in situ intestinal perfusion method was successfully applied to quantify the permeability of irinotecan and the exsorption of SN-38 in the same experiment, in a manner that robustly reflects real in vivo situation. P-gp inhibition using verapamil found to significantly enhance the intestinal permeability of irinotecan and potentially decrease the intestinal toxicity due to SN-38 exposure. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Circadian Variations in Exsorptive Transport: In Situ Intestinal Perfusion Data and In Vivo Relevance

2012 ◽  
Vol 29 (4) ◽  
pp. 443-453 ◽  
Author(s):  
Alper Okyar ◽  
Cornelia Dressler ◽  
Abeer Hanafy ◽  
Gül Baktir ◽  
Björn Lemmer ◽  
...  
Keyword(s):  
Intestinal Perfusion ◽  
Circadian Variations ◽  
In Situ Intestinal Perfusion

Underexpression of 4 Placenta-Associated MicroRNAs in Complete Hydatidiform Moles

2012 ◽  
Vol 22 (6) ◽  
pp. 1075-1080 ◽  
Author(s):  
Quan Na ◽  
Dan Wang ◽  
Weiwei Song
Keyword(s):  
In Situ Hybridization ◽  
Hydatidiform Mole ◽  
Polymerase Chain Reaction Analysis ◽  
Normal Pregnancy ◽  
Differentially Expressed ◽  
Control Group ◽  
Differentially Expressed Mirnas ◽  
Hydatidiform Moles

ObjectiveSeveral placental microRNAs (miRNAs) have been identified as placenta-associated miRNAs with the potential of estimating the condition of the placenta. However, our understanding of these miRNAs is limited. The aim of this study was to determine the expression of 8 placenta-associated miRNAs (miR-512-3p, miR-517a, miR-517b, miR-518b, miR-519a, miR-1185, miR-1283, and miR-1323) in complete hydatidiform mole (CHM).MethodsSamples were obtained from patients with CHM (CHM group, n = 12) and elective terminations of normal pregnancy (control group, n = 20). We detected differentially expressed placenta-associated miRNAs in placenta by quantitative real-time reverse transcriptase–polymerase chain reaction analysis. Subsequently, we assessed the expression location of differentially expressed miRNAs by in situ hybridization analysis.ResultsFour placenta-associated miRNAs (miR-517a, miR-517b, miR-518b, and miR-519a) were underexpressed in the CHM group, compared with the control group (P < 0.01). When further investigating these 4 miRNAs with regard to in vivo localization by in situ hybridization, we found that 2 miRNAs (miR-517b and miR-518b) were detected exclusively in the trophoblast layer, with little signal (if any) observed in villous stroma cells.ConclusionsThe results show that 4 miRNAs (miR-517a, miR-517b, miR-518b, and miR-519a) are deregulated in CHM, which suggests the involvement of these miRNAs in the functions of CHM placenta.

scholarly journals INFLUENCE OF P-GLYCOPROTEIN AND CYTOCHROME ISOENZYME-P3A4 ON BIOAVAILABILITY OF ANTICANCER DRUGS WITH CURCUMIN BY IN SITU INTESTINAL PERFUSION IN MALE WISTAR RATS

2019 ◽  
pp. 184-187
Author(s):  
MANOJ KANNA NALLA ◽  
SHANKARAIAH PULIGILLA
Keyword(s):  
Venous Blood ◽  
Hepatic Metabolism ◽  
Intestinal Perfusion ◽  
Hepatic Veins ◽  
Perfusion Technique ◽  
Flow Rates ◽  
P Glycoprotein ◽  
Drug Concentrations ◽  
In Situ Intestinal Perfusion

Objectives: An orally administered anticancer drug has been poor drug absorption; drug resistance and metabolism, which alters the bioavailability of drugs. An in situ intestine perfusion technique is developing under the different perfusion rates in the presence of drug inducers and inhibitors of cytochrome isoenzyme-P (CYP)-3A4 and P-glycoprotein (P-gp) for drug concentrations. Materials and Methods: The modified in situ intestinal perfusion technique was developed and followed to obtain the portal and hepatic venous blood samples paralleled at different perfusion time and flow rates of 0.05, 0.1, 0.5, and 1.0 mL/min using the imatinib (1 mg/mL) drug alone and in the presence of drug inducer and drug inhibitor for the period of 3 h. The imatinib drug concentrations were assayed using high-pressure liquid chromatography. Results: The results reveal that the mean imatinib drug concentrations in portal vein were higher than hepatic vein at various perfusion flow rates and time intervals were observed. The area under curve and plasma drug concentrations maximum of imatinib alone absorptions were significantly different between portal and hepatic veins (p<0.05) at the flow rates of 0.5 and 1.0 mL/min and also in the presence of drug inducer and inhibitors that indicating for the considerable hepatic involvement in the presystemic extraction or metabolism of drugs. Conclusions: The in situ perfusions approach could provide the useful tool for improving the basic understanding of absorption kinetics and hepatic metabolism of drugs in the presence of drug inducers and drug inhibitors (CYP3A4 and P-gp) under the development and facilitating the clinical applications.

Liquid-chromatographic determination of amoxapine and 8-hydroxyamoxapine in human serum.

1982 ◽  
Vol 28 (10) ◽  
pp. 2154-2157 ◽  
Author(s):  
J J Tasset ◽  
F M Hassan
Keyword(s):  
Internal Standard ◽  
Parent Drug ◽  
Chromatographic Determination ◽  
Solvent Mixture ◽  
Reversed Phase ◽  
Chromatographic Procedure ◽  
Liquid Chromatographic Determination ◽  
Toxic Concentrations ◽  
Liquid Chromatographic

Abstract We describe a liquid-chromatographic procedure for amoxapine and 8-hydroxyamoxapine, its active metabolite, in serum. We used a mu-Bondapak C18 reversed-phase column and a mobile phase of acetonitrile/water (74/26 by vol) plus 26 microL of n-butylamine per liter. The compounds were measured at 254 nm, with 8-methoxyloxapine as internal standard. Necessary pre-analysis purification consisted of adsorbing the drug from serum onto extraction columns, eluting with 1-butanol/hexane (1/5 by vol), re-extracting into aqueous acid, and from that re-extracting again into the elution-solvent mixture. We prefer this procedure for monitoring both therapeutic and toxic concentrations of amoxapine, because parent drug and metabolite are measured separately.

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