A dynamic in vitro lipolysis model: I. Controlling the rate of lipolysis by continuous addition of calcium

Determining the biliary clearance of drugs in humans is very challenging because bile is not readily accessible due to the anatomy of the hepatobiliary tract. The collection of bile usually is limited to postsurgical patients with underlying hepatobiliary disease. In healthy subjects, feces typically are used as a surrogate to quantify the amount of drug excreted via nonurinary pathways. Nevertheless, it is very important to characterize hepatobiliary elimination because this is a potential site of drug interactions that might result in significant alterations in systemic or hepatic exposure. In addition to the determination of in vivo biliary clearance values of drugs, the availability of in vitro models that can predict the extent of biliary excretion of drugs in humans may be a powerful tool in the preclinical stages of drug development. In this review, recent advances in the most commonly used in vivo methods to estimate biliary excretion of drugs in humans are outlined. Additionally, in vitro models that can be employed to investigate the molecular processes involved in biliary excretion are discussed to present an updated picture of the new tools and techniques that are available to study the complex processes involved in hepatic drug transport.

/pdf/methods-to-evaluate-biliary-excretion-of-drugs-in-humans-an-3fg6cy8ns6.pdf

Methods to evaluate biliary excretion of drugs in humans: an updated review.

Endoscopic Ultrasound-Guided Gallbladder Bile Aspiration in Idiopathic Pancreatitis Carries a Significant Risk of Bile Peritonitis

BACKGROUND: The physiological relevance of duodenal bile acids in the control of cholecystokinin release and pancreatic enzyme secretion is still unknown. AIMS: To provide a near physiological situation by perfusing a bile acid mixture mimicking the individual endogenous bile acid composition of the person under investigation. For maximal reduction of endogenous bile output the CCK-A receptor antagonist loxiglumide was infused intravenously. SUBJECTS AND METHODS: Seven healthy volunteers were studied on four different days by a duodenal marker perfusion technique. The individual bile acid composition in duodenal juice and test meal stimulated bile acid output was assessed on day 1. Bile acids were perfused at an amount of 30 or 100% as determined on day 1 in combination with the test meal in the presence or absence of loxiglumide. Pancreatic enzymes, bilirubin, and bile acid output were determined in duodenal juice. Plasma cholecystokinin (CCK) and plasma pancreatic polypeptide (PP) were measured radioimmunologically. RESULTS: Bile acid perfusion did not significantly alter stimulated pancreatic enzyme, bilirubin or bile acid output or plasma CCK. Loxiglumide did not alter basal CCK release but increased test meal stimulated CCK output fourfold (p

https://gut.bmj.com/content/gutjnl/39/5/661.full.pdf

Physiological control of cholecystokinin release and pancreatic enzyme secretion by intraduodenal bile acids.

https://www.gastrojournal.org/article/0016-5085(92)90848-S/pdf

The sequence of biliary events preceding the formation of gallstones in humans

In 10 patients with gall stone disease (eight women, two men; mean (SD) age 47.4 (13) years), bile was obtained by endoscopic aspiration after stimulation of the gall bladder with ceruletid and also by fine needle puncture of the gall bladder under local anaesthetic. The total lipid concentration of the puncture bile samples was mean (SD) 11.9 (4.7) g/dl, significantly higher than the endoscopic bile samples (3.9 (3.3) g/dl, p less than 0.001). Total bile acids, phospholipids, and biliary cholesterol (expressed in mol%) and cholesterol saturation index showed no significant differences between the two types of samples. The glycocholic acid concentration in the endoscopically obtained bile (27.7 (6.6) mol% v 23.3 (5.4) mol%; p less than 0.01) was significantly higher than the puncture bile samples. Puncture bile exhibited a significantly shorter nucleation time (3.5 (3.3) days v 19.6 (11.9) days; p less than 0.001). For determination of the nucleation time, endoscopic bile aspiration after gall bladder stimulation with ceruletid led to adequately concentrated samples in 50% of the study subjects. Cholesterol monohydrate crystal formation in native bile was observed in six samples of puncture bile and in three samples of the endoscopically obtained bile. The presence of cholesterol crystals and the determination of nucleation time in the puncture bile were the best discriminants between cholesterol and pigment gall stones and correlated well with computed tomogram analysis.

https://gut.bmj.com/content/gutjnl/31/12/1407.full.pdf

Comparison of gall bladder bile and endoscopically obtained duodenal bile.

Computed tomography facilitates an in vivo classification of gallstones and can aid in the identification of calcifications that escape detection with conventional radiologic procedures. Of patients with radiolucent stones, 54.8% exhibited calcifications either in the form of discrete rims (41.9%) or at the center of the stone (12.9%). Densities of the noncalcified areas of partially calcified stones averaged 40.68±6.8 Hounsfield units (HU), which was not significantly higher than the average of 31.85±3.19 HU for noncalcified stones. Calcified regions showed significantly higher densities (240.0±28.6 HU,p< 0.001,x ± SEM). Of the identified stones, 16.1% showed densities greater than 50 HU. These were primarily bilirubin stones, which cannot yet be treated successfully with conservative therapeutic modalities.

Computed tomography evaluation of radiolucent gallstones in vivo.

Radiographic aspects in transcatheter contact dissolution of calcified gallbladder concrements

Seit der Einfuhrung konservativer Behandlungsmoglichkeiten von Gallenblasensteinen durch Gallensaurelyse, extrakorporale Stoswellenlithotripsie oder lokale Litholyse ruckt die nicht invasive, praetherapeutische Steindifferenzierung in den Mittelpunkt des diagnostischen Interesses, da die meisten nicht operativen Behandlungsverfahren nur bei Cholesterinsteinen angewandt werden konnen. Die konventionelle B-Bild-Ultraschalldiagnostik ist, trotz spezifischer Darstellungsmoglichkeiten, nicht mit ausreichender Sicherheit in der Lage, Cholesterin- von Pigmentsteinen zu trennen [1]. Bisher wurden zur Bestimmung des Kalkgehaltes von Konkrementen deshalb computertomographische Messungen der Steindichte in Hounsfield Einheiten (HU) durchgefuhrt [2]. Da dieses Verfahren relativ aufwendig und teuer ist, versuchten wir durch spezielle Signalaufbereitungstechniken des konventionellen Ultraschallsignals weitere Aufschlusse uber die Steinzusammensetzung zu erhalten. Nachdem die ersten in vitro Ergebnisse dieser Hochfrequenzsignalanalyse (HF) vielversprechend schienen [3], verwendeten wir einen Prototyp dieses Gerates im klinischen Routineeinsatz. Als Referenzmethode diente die Computertomographie (CT), wobei wir Steine mit uber 100 HU als kalzifizierte Pigmentsteine und Konkremente mit Dichtewerten unter 100 HU als Cholesterinsteine definierten.

In vivo HF-Signalanalyse von Gallensteinen zur Differenzierung von Cholesterin- und Pigmentkonkrementen

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Comparison of gall bladder bile and endoscopically obtained duodenal bile.

Computed tomography evaluation of radiolucent gallstones in vivo.

Radiographic aspects in transcatheter contact dissolution of calcified gallbladder concrements

In vivo HF-Signalanalyse von Gallensteinen zur Differenzierung von Cholesterin- und Pigmentkonkrementen