Ethanol and drug interactions

2000 ◽  
Vol 57 (4) ◽  
pp. 220-226 ◽  
Author(s):  
Oneta
Keyword(s):  
Drug Interactions ◽  
Zytochrom P450 ◽  
First Pass

Der Alkoholstoffwechsel findet vor allem in der Leber statt. Dabei spielt beim Alkoholabstinenten die Alkoholdehydrogenase (ADH) die wichtigste Rolle. Beim chronischen Trinker hingegen gewinnt der Alkoholabbauweg über das mikrosomale Äthanol-oxidierende System (MEOS), insbesondere über das Zytochrom P450 2E1, infolge Induktion ganz entscheidend an Bedeutung. Es kann in dieser Situation vier- bis zehnmal mehr Alkohol metabolisieren. Da das mikrosomale Enzymsystem neben Alkohol auch diverse Medikamente verstoffwechselt, wird es zum Spielball für klinisch bedeutsame Alkohol-Medikamenten Interaktionen. Die klinisch relevanten Interaktionen werden abgehandelt. Im weiteren wird auf die Bedeutung des sogenannten First-pass Stoffwechsels im Magen eingegangen. Der einzige Weg zur Verhinderung schwerwiegender Alkohol-Medikamenten Interaktionen ist die Verbreitung deren Kenntnis sowohl unter Ärzte als auch Patienten.

scholarly journals Lack of Indinavir Effects on Methadone Disposition Despite Inhibition of Hepatic and Intestinal Cytochrome P4503A (CYP3A)

2012 ◽  
Vol 116 (2) ◽  
pp. 432-447 ◽  
Author(s):  
Evan D. Kharasch ◽  
Pamela Sheffels Bedynek ◽  
Christine Hoffer ◽  
Alysa Walker ◽  
Dale Whittington
Keyword(s):  
Plasma Concentration ◽  
Drug Interactions ◽  
Plasma Concentrations ◽  
Antiretroviral Drugs ◽  
Cyp3a Activity ◽  
Oral Clearance ◽  
Hepatic Extraction ◽  
Time Curve ◽  
Apparent Oral Clearance ◽  
First Pass

Background Methadone disposition and pharmacodynamics are highly susceptible to interactions with antiretroviral drugs. Methadone clearance and drug interactions have been attributed to cytochrome P4503A4 (CYP3A4), but actual mechanisms are unknown. Drug interactions can be clinically and mechanistically informative. This investigation assessed effects of the protease inhibitor indinavir on methadone pharmacokinetics and pharmacodynamics, hepatic and intestinal CYP3A4/5 activity (using alfentanil), and intestinal transporter activity (using fexofenadine). Methods Twelve healthy volunteers underwent a sequential crossover. On three consecutive days they received oral alfentanil plus fexofenadine, intravenous alfentanil, and intravenous plus oral (deuterium-labeled) methadone. This was repeated after 2 weeks of indinavir. Plasma and urine analytes were measured by mass spectrometry. Opioid effects were measured by miosis. Results Indinavir significantly inhibited hepatic and first-pass CYP3A activity. Intravenous alfentanil systemic clearance and hepatic extraction were reduced to 40-50% of control, apparent oral clearance to 30% of control, and intestinal extraction decreased by half, indicating 50% and 70% inhibition of hepatic and first-pass CYP3A activity. Indinavir increased fexofenadine area under the plasma concentration-time curve 3-fold, suggesting significant P-glycoprotein inhibition. Indinavir had no significant effects on methadone plasma concentrations, methadone N-demethylation, systemic or apparent oral clearance, renal clearance, hepatic extraction or clearance, or bioavailability. Methadone plasma concentration-effect relationships were unaffected by indinavir. Conclusions Despite significant inhibition of hepatic and intestinal CYP3A activity, indinavir had no effect on methadone N-demethylation and clearance, suggesting little or no role for CYP3A in clinical disposition of single-dose methadone. Inhibition of gastrointestinal transporter activity had no influence of methadone bioavailability.

Embedding Procedure for Water Swollen Samples

1970 ◽  
Vol 28 ◽  
pp. 504-505
Author(s):  
Ann M. Thomas ◽  
Virginia Shemeley
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Ion Exchange ◽  
Structural Changes ◽  
Cross Linking ◽  
Ion Exchange Resins ◽  
Transmission Electron ◽  
First Pass ◽  
Exchange Resins

Those samples which swell rapidly when exposed to water are, at best, difficult to section for transmission electron microscopy. Some materials literally burst out of the embedding block with the first pass by the knife, and even the most rapid cutting cycle produces sections of limited value. Many ion exchange resins swell in water; some undergo irreversible structural changes when dried. We developed our embedding procedure to handle this type of sample, but it should be applicable to many materials that present similar sectioning difficulties.The purpose of our embedding procedure is to build up a cross-linking network throughout the sample, while it is in a water swollen state. Our procedure was suggested to us by the work of Rosenberg, where he mentioned the formation of a tridimensional structure by the polymerization of the GMA biproduct, triglycol dimethacrylate.

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