Biliary excretion of antibiotics in man.

Acocella, G; Mattiussi, R; Nicolis, F. B.; Pallanza, R; Tenconi, L. T.

doi:10.1136/gut.9.5.536

Cited by 54 publications

(21 citation statements)

References 16 publications

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“…Typically, patients are administered the drug of interest prior to surgery, and the amount of drug found in the gallbladder after removal is quantified. 5,6 This approach only allows a single time point determination of drug content in bile. More commonly, studies employ patients that require a temporary bile shunt (Ttube) that diverts bile from the liver to a transcutaneous port for external collection.…”

Section: Introductionmentioning

confidence: 99%

A novel method for the determination of biliary clearance in humans

Ghibellini

Johnson

Kowalsky

et al. 2004

AAPS J

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Biliary excretion is an important route of elimination and the biliary tract is a potential site of toxicity for many drugs and xenobiotics. Quantification of biliary excretion in healthy human volunteers is logistically challenging and is rarely defined during drug development. The current study uses a novel oroenteric tube coupled with a specialized clinical protocol to examine the pharmacokinetics of 99m Technetium (Tc-99m) mebrofenin, a compound that undergoes rapid hepatic uptake and extensive biliary excretion. A custommade multilumen oroenteric tube was positioned in the duodenum of healthy human volunteers. Subjects were positioned under a gamma camera and 2.5 mCi of Tc-99m mebrofenin was administered intravenously. Duodenal aspirates, blood samples, and urine were collected periodically for 3 hours. Two hours after Tc-99m mebrofenin administration, the gallbladder was contracted with an intravenous infusion of cholecystokinin-8. Gamma scintigraphy was used to determine the gallbladder ejection fraction in each subject. Total systemic clearance of Tc-99m mebrofenin approximated liver blood flow (Cl total 17.3 ± 1.7 mL/min/kg), and 35% to 84% of the Tc-99m mebrofenin dose was recovered in bile. However, when the data were corrected for the gallbladder ejection fraction, 71% to 92% of the excreted Tc-99m mebrofenin dose was recovered. This novel oroenteric tube and clinical protocol provide a useful method to quantify biliary excretion of xenobiotics in healthy human volunteers.

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Section: Introductionmentioning

confidence: 99%

A novel method for the determination of biliary clearance in humans

Ghibellini

Johnson

Kowalsky

et al. 2004

AAPS J

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“…Variable ampicillin excretion in bile has been noted in some reports (Bullock 1961;Ayliffe & Davies, 1965;Acocella et al, 1968), but this was not confirmed in a recent study in which no ampicillin was detected in pure bile aspirated directly from the common bile duct by endoscopic retrograde cholangiography (Roberts & Williams, 1979).…”

Section: Discussionmentioning

confidence: 86%

“…Collection of bile by direct gallbladder puncture at laparotomy or by ttube drainage would have yielded higher concentrations for both drugs but these techniques were not suitable for our study carried out in normal subjects. It is unlikely that either of the drugs used in our study would have altered the composition or flow of bile since ampicillin and cephalosporins have been shown to have no effect on bilirubin and cholesterol saturation or on volume of bile collected by t-tube drainage (Acocella et al, 1968). The variable drug concentrations noted in bile probably represent the effect of intermittent gallbladder emptying (Mack & Todd, 1968).…”

Section: Discussionmentioning

confidence: 99%

Biliary excretion of amoxycillin and ceftriaxone after intravenous administration in man.

Maudgal¹,

Maxwell²,

Lees³

et al. 1982

Brit J Clinical Pharma

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1 Plasma and biliary concentrations of amoxycillin and ceftriaxone were measured after bolus intravenous administration (500 mg) in four subjects with normal hepato-biliary and renal function.2 The mean plasma elimination half-life for ceftriaxone (ty½ = 330 + 30 min) was considerably longer than that for amoxycillin (ty, = 60 + 9 min).3 The biliary concentration of ceftriaxone was above plasma concentration of the drug throughout the study period, whereas amoxycillin concentration in the bile was lower than that in plasma. 4 Both plasma and biliary concentrations of ceftriaxone were substantially higher than previously determined minimum inhibitory concentration (MIC) values for E. coli (and several other common biliary tract pathogens) for over 6 h following drug administration. Amoxycillin concentration in plasma fell below MIC by 2 h, and did not reach inhibitory concentrations in bile.

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“…Liver disease is known to affect the handling of these second-category drugs, but with the exception of chloramphenicol, the change in dosing requirements in liver disease is not clear. Liver disease decreases the biliary concentrations of drug normally concentrated in the bile, such as erythromycin, ampicillin, nafcillin, and cefamandole (1). Little data is available relating the type of liver disease to the differences in the handling of these antibiotics (3).…”

Section: Resultsmentioning

confidence: 99%

“…first category are such drugs as ampicillin, mezlocillin, carbenicillin (22), and certain other penicillin derivatives, including cephalothin, cefamandole, clindamycin, and erythromycin (1,8,10,13). The second category of drugs handled by the liver include rifampin, chloramphenicol, and isoniazid.…”

Section: Resultsmentioning

confidence: 99%

Effects of cirrhosis on kinetics of aztreonam

MacLeod¹,

Bartley²,

Payne³

et al. 1984

Antimicrob Agents Chemother

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Aztreonam was administered as a single, 3-min, 1-g intravenous infusion to 18 subjects, including 6 with biopsy-proven, primary biliary cirrhosis, 6 with biopsy-proven, stable alcoholic cirrhosis, and 6 age-and sexmatched control subjects with normal hepatic functions. Aztreonam was well tolerated by all subjects. Multiple blood samples and timed, cumulative urine samples were taken for assay of aztreonam content and determination of pharmacokinetic profiles. Protein-free filtrates of serum were also assayed for drug levels. Analyses by microbiological and high-pressure liquid chromatographic procedures gave equivalent results. The kinetic data were described by an open, linear, two-compartment model. There were significant differences in elimination half-life (3.2 verus 1.9 h), serum clearance (0.8 versus 1.1 ml/min per kg), and nonrenal clearance (0.2 versus 0.4 ml/min per kg) between the alcoholic cirrhosis group and the normal control group and in elimination half-life (2.2 versus 1.9 h) between the primary biliary cirrhosis group and the normal control group. There was also a difference in nonrenal clearance between the alcoholic cirrhosis and primary biliary cirrhosis groups (0.2 versus 0.5 ml/min per kg). Although the handling of aztreonam differed in the three groups, the magnitude of the difference would warrant a change in aztreonam dosing only for the alcoholic cirrhosis group. In this group, dose adjustment might be required if long-term therapy with high doses of aztreonam is indicated.

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Biliary excretion of antibiotics in man.

Cited by 54 publications

References 16 publications

A novel method for the determination of biliary clearance in humans

A novel method for the determination of biliary clearance in humans

Biliary excretion of amoxycillin and ceftriaxone after intravenous administration in man.

Effects of cirrhosis on kinetics of aztreonam

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