Excretion of Antibiotics in Pancreatic Fluid

Preston, Frederick W.; Silverman, Milton; Henegar, George C.

doi:10.1001/archsurg.1959.04320050141021

Cited by 15 publications

(5 citation statements)

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“…This has some resemblance to the change in "barrier" mechanism that exists for the transport of antibiotics into the cerebrospinal fluid in normal animals and in animals with induced meningitis. Pharmacological studies performed with other antibiotic agents demonstrated absence of tetracyclines and penicillins in the pancreatic fluid after systemic administration (14,16), the presence of inadequate concentrations of streptomycin and chloramphenicol (14,16), and the presence of adequate concentrations of erythromycin (14), clindamycin (15), and sulfonamides in this fluid (9). The alkaline pH of the pancreatic fluid may in addition change the antimicrobial activity of various drugs.…”

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confidence: 99%

Effect of pancreatitis on ampicillin excretion in pancreatic fluids of dogs

Rubinstein¹,

Haspel²,

Klein³

et al. 1980

Antimicrob Agents Chemother

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Pancreatic excretion of ampicillin was evaluated in normal dogs and in dogs with induced pancreatitis. A 100-mg/kg ampicillin dose administered intravenously induced mean peak serum levels of 100 ,ig/ml, and a 200-mg/kg intravenous dose induced a mean peak serum level of 273 ,ug/ml. Ampicillin serum levels did not differ between the group of nornal dogs and those with pancreatitis. In normal dogs, the peak pancreatic fluid ampicillin concentration after the 100-mg/ kg dose was 0.4 ,ug/ml, and that after the 200-mg/kg dose was 2.7 ,ug/ml. In dogs with pancreatitis, the mean peak ampicillin concentration in the pancreatic fluid after the 100 mg/kg dose was 19,ug/ml, and that after the 200-mg/kg dose was 38.5 ,ug/ml. Pancreatic fluid ampicillin concentrations were therapeutic in dogs with pancreatitis and subtherapeutic in normal dogs.Pancreatitis is a disease associated with a considerable rate of infectious complications (3,7, 20). Pancreatic abscess is the most common local septic complication (2, 7), bearing a high rate of morbidity and mortality (10,18). This clinical situation has led to a number of experimental and clinical trials of prophylactic antibiotic regimens aimed at reducing the grave sequelae of pancreatitis. Ampicillin was the agent chosen for the current study because it is active against most enteric organisms responsible for pancreatic abscess and because it achieves high serum and bile concentrations (11). Since we could not find any information concerning the concentration of ampicillin in the pancreatic fluid, we undertook an investigation in which we measured the concentrations of ampicillin in the serum and pancreatic juice of normal dogs and dogs with induced pancreatitis after the intravenous administration of the drug.(The paper was presented in part at the 11th Intemational Congress of Chemotherapy, Boston, Mass., 1979.) MATERIALS AND METHODS Twelve mongrel dogs weighing 16 to 20 kg each underwent laparotomy. The accessory pancreatic duct was identified, ligated, and transected. A modified Thomas cannula was inserted in the duodenum exactly opposite the orifice of the main pancreatic duct. Another modified Thomas cannula was inserted into the most dependent part of the stomach as described by Bayer et al. (1). Dogs were allowed to recover for 3 weeks after the operation; they received regular food and water ad lib.Each dog was deprived of food, but not water, for 18 h before the experiment. The duodenal and gastric cannulas remained open during each experiment. The main pancreatic duct was cannulated with a glass cannula, and the pancreatic juice was collected through it. Secretin (Sigma S-3250) was infused at a rate of 0.03 U/kg per min to secure constant pancreatic juice flow throughout the experiment. After 15 min, blood, pancreatic juice, and gastric juice were collected. Ampicillin was then administered intravenously in fast infusion (over 10 min). Seven dogs received 200 mg/kg, and five dogs received 100 mg/kg. Blood, gastric juice, and pancreatic juice were obtained at 15, 30,...

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confidence: 99%

Effect of pancreatitis on ampicillin excretion in pancreatic fluids of dogs

Rubinstein¹,

Haspel²,

Klein³

et al. 1980

Antimicrob Agents Chemother

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Section: Discussionmentioning

confidence: 86%

“…Absent penetration into the pancreatic fluid of ampicillin, penicillin, and tetracycline, has been previously reported [15,17,18]. Chloramphenicol and streptomycin reached subtherapeutic levels in the pancreatic juice, following systematic administration [17,18]. On the other hand, sulfonamides, clindamycin, and erythromycin were present in adequate concentrations in the pancreatic fluid of man and experimental animals [10,17,19].…”

Section: Discussionmentioning

confidence: 86%

“…Chloramphenicol and streptomycin reached subtherapeutic levels in the pancreatic juice, following systematic administration [17,18]. On the other hand, sulfonamides, clindamycin, and erythromycin were present in adequate concentrations in the pancreatic fluid of man and experimental animals [10,17,19]. In this patient, a single 600 mg clindamycin dose, administered intravenously, produced a peak serum concentration of 37 mcg/ml and a peak pancreatic fluid concentration of 1.8 mcg/ml that occurred 120 min following the dose.…”

Section: Discussionmentioning

confidence: 94%

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Effect of pancreatitis on moxalactam excretion in pancreatic fluids of dogs and man

et al. 1988

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Pancreatic excretion of moxalactam was evaluated in a patient with mild pancreatitis and pancreatic fistula, in normal dogs, and in dogs with induced pancreatitis. In the patient, m0xalactam was not excreted in the pancreatic fluid, despite adequate blood levels. Similarly, no moxalactam activity was present in the pancreatic fluids of normal animals and animals with experimentally induced pancreatitis. The data suggest that moxalactam does not penetrate into pancreatic fluid in detectable concentrations in the presence or absence of pancreatic inflammation.These results suggest the need for further study of the use of moxalactam in the treatment of bacterial infections of the pancreas.

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“…The selective secretion of some antibiotics into PES after intravenous administration has been long recognized [10,[34][35][36][37], with some antibiotics reaching concentrations in PES that are up to four-fold higher than in plasma. The higher concentrations of the chemotherapeutic agent 5-fluoruracil in PES relative to plasma [38] is another example of the capability of the pancreas ductal epithelium to selectively concentrate some therapeutic compounds in PES.…”

Section: Discussionmentioning

confidence: 99%

Selective and Concentrative Enteropancreatic Recirculation of Antibiotics by Pigs

Buddington,

Pierzynowski,

Holmes

et al. 2023

Antibiotics

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Antibiotics that are efficacious for infectious pancreatitis are present in pancreatic exocrine secretion (PES) after intravenous administration and above minimal inhibitory concentrations. We measured concentrations of four antibiotics by tandem liquid chromatography–mass spectroscopy in plasma and PES after enteral administration to juvenile pigs with jugular catheters and re-entrant pancreatic-duodenal catheters. Nystatin, which is not absorbed by the intestine nor used for infectious pancreatitis (negative control), was not detected in plasma or PES. Concentrations of amoxicillin increased in plasma after administration (p = 0.035), but not in PES (p = 0.51). Metronidazole and enrofloxacin that are used for infectious pancreatitis increased in plasma after enteral administration and even more so in PES, with concentrations in PES averaging 3.1 (±0.5)- and 2.3 (±0.6)-fold higher than in plasma, respectively (p′s < 0.001). The increase in enrofloxacin in PES relative to plasma was lower after intramuscular administration (1.8 ± 0.5; p = 0.001). The present results demonstrate the presence of a selective and concentrative enteropancreatic pathway of secretion for some antibiotics. Unlike the regulated secretion of bile, the constitutive secretion of PES and intestinal reabsorption may provide a continuous exposure of pancreas tissue and the small intestine to recirculated antibiotics and potentially other therapeutic molecules. There is a need to better understand the enteropancreatic recirculation of antibiotics and the associated mechanisms.

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Excretion of Antibiotics in Pancreatic Fluid

Cited by 15 publications

References 5 publications

Effect of pancreatitis on ampicillin excretion in pancreatic fluids of dogs

Effect of pancreatitis on ampicillin excretion in pancreatic fluids of dogs

Effect of pancreatitis on moxalactam excretion in pancreatic fluids of dogs and man

Selective and Concentrative Enteropancreatic Recirculation of Antibiotics by Pigs

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