Changes of Drug Pharmacokinetics in Patients with Short Bowel Syndrome: A Systematic Review

Hong, Wallace Bok-Thoe; Tan, Wee Kiat; Law, Lawrence Siu-Chun; Ong, David E.; Lo, Elaine Ah-Gi

doi:10.1007/s13318-021-00696-y

Cited by 14 publications

(14 citation statements)

References 75 publications

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“…In a systematic review of drug absorption in adult patients with SBS-IF, most of the medications (29 of 37) had decreased absorption, and some lost therapeutic effect entirely. 19 Depending on drug metabolism, the presence of a colon in continuity may affect pharmacokinetics as a potentially important site for absorption and possible enterohepatic circulation of the drug and/or metabolites. In this study, we found substantially decreased SEFA-6179 absorption in both SBS-IF models, with the greatest decrease in the pseudojejunostomy group with near-complete bypass of the colon.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with SBS‐IF, unpredictable absorption often results in avoidance of enteral drug administration in favor of alternative routes (parenteral, sublingual, subcutaneous, etc). In a systematic review of drug absorption in adult patients with SBS‐IF, most of the medications (29 of 37) had decreased absorption, and some lost therapeutic effect entirely 19 . Depending on drug metabolism, the presence of a colon in continuity may affect pharmacokinetics as a potentially important site for absorption and possible enterohepatic circulation of the drug and/or metabolites.…”

Section: Discussionmentioning

confidence: 99%

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Absorption of an engineered medium‐chain fatty acid analogue in two short bowel syndrome minipig models

Fligor,

Tsikis,

Hirsch

et al. 2023

J Parenter Enteral Nutr

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BackgroundEnteral drug therapy is challenging in short bowel syndrome with intestinal failure (SBS‐IF) because of unpredictable absorption. SEFA‐6179 is an enterally administered medium‐chain fatty acid analogue under development for intestinal failure–associated liver disease. We investigate the pharmacokinetics of two SEFA‐6179 formulations in two large‐animal models of SBS‐IF, including a new pseudojejunostomy model.MethodsTwenty Yucatan minipigs were obtained. Half underwent pre‐resection pharmacokinetic study with single‐dose SEFA‐6179 administration. All minipigs then underwent 90% jejunoileal resection, with either a jejunoileal anastomosis or bypass of the intraperitoneal colon with anastomosis just proximal to the rectum (pseudojejunostomy). On postoperative day 3, a single‐dose pharmacokinetic study was performed.ResultsBoth SBS‐IF models were well tolerated. Compared with the jejunoileal anastomosis minipigs, pseudojejunostomy minipigs had a more severe malabsorptive phenotype with weight loss by postoperative day 4 (+0.1 vs −0.9 kg, P = 0.03) and liquid diarrhea (Bristol 5 vs Bristol 7, P = 0.0007). Compared with pre‐resection minipigs, both jejunoileal and pseudojejunostomy minipigs had lower total plasma exposure of SEFA‐6179 measured by area under the curve (jejunoileal: 37% less, P = 0.049; pseudojejunostomy: 74% less, P = 0.0001). Peak plasma concentration was also lower in the pseudojejunostomy group compared with pre‐resection (65% less, P = 0.04), but not lower in the jejunoileal group (P = 0.47).ConclusionIn two SBS‐IF minipig models, SEFA‐6179 had substantially decreased absorption compared with pre‐resection minipigs. Dose optimization for different intestinal anatomy and function may be required. We describe a new SBS‐IF pseudojejunostomy model that may improve the translation of preclinical research to patients with SBS‐IF who have enterostomies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Absorption of an engineered medium‐chain fatty acid analogue in two short bowel syndrome minipig models

Fligor,

Tsikis,

Hirsch

et al. 2023

J Parenter Enteral Nutr

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“…SBS can also negatively affect the absorption of orally administered drugs. The extent of malabsorption is drug‐specific and depends on the site of drug absorption in the digestive tract, and the extent and location of intestinal resection 2 . In cancer patients receiving oral targeted antineoplastic drugs, individualized dose adjustments are often recommended and are particularly useful for drugs with established exposure–response and/or exposure–toxicity relationships 3 if interindividual pharmacokinetic (PK) variability is large.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic drug monitoring of osimertinib in non‐small cell lung cancer and short bowel syndrome: A case report

Longuespée,

Kunz,

Fresnais

et al. 2023

Brit J Clinical Pharma

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Short bowel syndrome (SBS) following extensive intestinal resection is often characterized by impaired absorption of orally administered drugs, including tyrosine kinase inhibitors (TKI). We report the case of a patient with EGFR‐mutated non‐small cell lung carcinoma treated with 80 mg/day of the TKI osimertinib who achieved partial response of the tumour, but was subsequently subjected to a double‐barrelled jejunostomy due to ileus. Due to the development of SBS after the bypass surgery, plasma concentrations of osimertinib were monitored using mass spectrometry. The therapeutic drug monitoring confirmed a malabsorption of osimertinib in the patient (108 ng/mL, which is below the 5th percentile of the expected plasma concentration) and was useful to guide adjustments of TKI dosing in order to achieve adequate blood levels (161 ng/mL after increase of the dose to 120 mg/day) in order to maintain tumour control.

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confidence: 99%

“…This can affect not only IBD patients but also many other patients suffering from malabsorption. 8 These patients should be aware of the risk, and a different birth control method should be considered. 9 Other aspects include management of patients with chronic disease exacerbation during pregnancy -this involves not only IBD, but also patients with chronic liver disease and other chronic conditions -what should be our treatment limitations?…”

mentioning

confidence: 99%

US supreme court decision: the gastroenterological perspective

Lahat

Klang

2022

Therap Adv Gastroenterol

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Changes of Drug Pharmacokinetics in Patients with Short Bowel Syndrome: A Systematic Review

Cited by 14 publications

References 75 publications

Absorption of an engineered medium‐chain fatty acid analogue in two short bowel syndrome minipig models

Absorption of an engineered medium‐chain fatty acid analogue in two short bowel syndrome minipig models

Therapeutic drug monitoring of osimertinib in non‐small cell lung cancer and short bowel syndrome: A case report

US supreme court decision: the gastroenterological perspective

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