valacyclovir and Colitis

Topics: Aged; Antiviral Agents; Colitis; Colonic Diseases; Colonoscopy; Colostomy; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Infusions, Intravenous; Intestinal Fistula; Valacyclovir

A 42-year-old woman with a history of cholangiocarcinoma on adjuvant chemotherapy with capecitabine presented with painless haematochezia. She was found to have an isolated twenty-five mm ulcer in the ascending colon. Biopsies of the ulceration demonstrated typical cytomegalovirus (CMV) inclusions and her peripheral blood CMV PCR was significantly elevated. This is an unusual case of a solitary proximal colon ulcer. Non-steroidal anti-inflammatory drugs, inflammatory bowel disease and malignancy, are the most frequent causes of isolated ulcers in the proximal colon. Gastrointestinal (GI) CMV disease most commonly causes CMV colitis and is considered rare outside of the transplant population and other severely immunosuppressed patient groups. Patients who have received chemotherapy may also be at risk for GI CMV disease. The diagnosis should be suspected in patients who present with haematochezia or watery diarrhoea within a broad window of time after receiving chemotherapy.

Topics: Adult; Antimetabolites, Antineoplastic; Antiviral Agents; Bile Duct Neoplasms; Capecitabine; Chemotherapy, Adjuvant; Cholangiocarcinoma; Colitis; Colon, Ascending; Cytomegalovirus Infections; Female; Gastrointestinal Hemorrhage; Humans; Immunocompromised Host; Pancreaticoduodenectomy; Risk Factors; Ulcer; Valacyclovir

Topics: Acyclovir; Antiviral Agents; Azathioprine; Colitis; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Immunosuppressive Agents; Valacyclovir; Valine; Young Adult

The effect of colitis induced with dextran sodium sulfate (DSS) in rats on the bioavailability of drugs transported by the oligopeptide transporter PepT-1 was analyzed by studying the pharmacokinetics of PepT-1 substrates: cephalexin and valacyclovir, the prodrug of antiviral acyclovir. Western blot, immunohistochemistry, and real-time PCR were used to determine the PepT-1 protein and gene expression. We observed (1) no significant modification of PepT-1 expression in the duodenum and jejunum; (2) a slight decrease in both PepT-1 mRNA (50%) and protein expression (25%) in the ileum following DSS challenge; and (3) ectopic PepT-1 immunostaining in regenerative hyperplasia segments in the distal colon from DSS-treated rats where focal inflammation is localized. However, no modification of pharmacokinetic parameters (C (max), T (max), AUC) of cephalexin or acyclovir was detected. In conclusion, DSS-induced rat colitis did not alter PepT-1 substrate bioavailability despite certain modifications in PepT-1 expression profile.

Topics: Acyclovir; Animals; Anti-Bacterial Agents; Antiviral Agents; Biological Availability; Cephalexin; Colitis; Immunohistochemistry; Intestinal Mucosa; Male; Peptide Transporter 1; Rats; Rats, Wistar; RNA, Messenger; Symporters; Valacyclovir; Valine