valganciclovir and Fever

As a result of the low oral bioavailability of ganciclovir, a prodrug was developed to improve the bioavailability of ganciclovir. This study was designed to investigate the fasting, single-dose pharmacokinetics as well as the absolute and relative bioavailability of a valine ester prodrug of ganciclovir, valganciclovir, as compared to oral and intravenous ganciclovir in asymptomatic HIV+ and CMV+ subjects. In this open-label, randomized, three-period crossover study, 18 subjects received, in random order, single oral doses of valganciclovir 360 mg and ganciclovir 1000 mg and an intravenous infusion of ganciclovir 5 mg/kg over 1 hour. Valganciclovir was rapidly and extensively hydrolyzed to ganciclovir, resulting in significantly greater bioavailability compared to 1000 mg oral ganciclovir (60.9% vs. 5.6%, respectively). Higher peak serum concentrations were reached earlier following valganciclovir (ganciclovir [2.98 +/- 0.77 micrograms/mL at 1.0 +/- 0.3 h]) than following oral ganciclovir (0.47 +/- 0.17 microgram/mL and 2.2 +/- 1.0 h). Mean total ganciclovir AUCs following oral ganciclovir (1000 mg) and 360 mg valganciclovir (3.8 +/- 1.2 and 10.8 +/- 1.9 micrograms-h/mL) were less than that following a standard 5 mg/kg intravenous infusion of ganciclovir (25.1 +/- 3.8 micrograms-h/mL). In summary, valganciclovir is a prodrug with a favorable safety profile with enhanced bioavailability and significantly higher serum concentrations of ganciclovir than following oral administration of ganciclovir itself.

Topics: Adult; Anti-HIV Agents; Antiviral Agents; Area Under Curve; Biological Availability; Cross-Over Studies; Cytomegalovirus Infections; Diarrhea; Dizziness; Dyspnea; Exanthema; Female; Fever; Ganciclovir; Headache; HIV Seropositivity; Humans; Hypertension; Male; Metabolic Clearance Rate; Middle Aged; Pain; Prodrugs; Syncope; Valganciclovir

We present the case of a 28-year-old man with recently-diagnosed human immunodeficiency virus and hepatitis C virus infection. He developed obstructive cholangiopathy secondary to cytomegalovirus and Kaposi sarcoma, both diagnosed by endoscopic retrograde cholangiopancreatography and biopsies. He received antiretroviral therapy, chemotherapy and valganciclovir with full recovery.

Topics: Abdominal Pain; Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Bile Duct Diseases; Biopsy; Cholangiopancreatography, Endoscopic Retrograde; Cytomegalovirus; Diarrhea; Fever; Hepatitis C; HIV Infections; Humans; Male; Sarcoma, Kaposi; Valganciclovir; Weight Loss

Thrombotic thrombocytopenic purpura (TTP) is a rare, potentially fatal disease with multisystem involvement. Cytomegalovirus (CMV) infection as a cause of refractory TTP, has been reported only in immunocompromised individuals. We report a case of CMV-induced refractory TTP in an immunocompetent individual.. A 35-year-old, previously healthy Sri Lankan man, presented with fever for 3 days with gum bleeding and progressive drowsiness. His Glasgow coma scale score was 10/15. He did not have papilloedema or neck stiffness. Laboratory evaluation showed a severe thrombocytopenia with microangiopathic haemolytic anaemia. There was marginal renal impairment and normal coagulation profile. Non-contrast CT scan of brain was normal. A diagnosis of thrombotic thrombocytopenic purpura was made. Despite daily plasma exchanges and high-dose steroids, he failed to achieve the expected therapeutic response, thus demonstrating refractory TTP. On exploring for possible causes of refractoriness to treatment, a clinically significant PCR titre of CMV was detected. Treatment of CMV infection lead to complete recovery of TTP. His disease course was further complicated with spontaneous spinal haemorrhage leading to neurological sequelae.. This is the first report of CMV induced refractory TTP in an immunocompetent adult. It is also the first report of clinically significant spontaneous spinal haematoma in TTP. These two rare occurrences should be considered when patients with refractory TTP do not improve as expected.

Topics: Adult; Anemia, Hemolytic; Antiviral Agents; Cytomegalovirus Infections; Fever; Humans; Immunocompetence; Male; Purpura, Thrombotic Thrombocytopenic; Valganciclovir

Topics: Angiography; Antiviral Agents; Azathioprine; Cecum; Crohn Disease; Digestive System Surgical Procedures; Disease Progression; Female; Fever; Foscarnet; Ganciclovir; Gastrointestinal Hemorrhage; Humans; Ileitis; Ileum; Immunosuppression Therapy; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation; Male; Pancytopenia; Rectum; Treatment Outcome; Valganciclovir; Young Adult

Topics: Antiviral Agents; Cytomegalovirus Infections; Female; Fever; Ganciclovir; Humans; Immunocompetence; Middle Aged; Splenic Infarction; Valganciclovir

Valganciclovir is a prodrug of ganciclovir which has been developed for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. Oral valganciclovir is rapidly absorbed and hydrolysed to ganciclovir. The oral bioavailability of ganciclovir after oral valganciclovir administration is high. Oral valganciclovir 900 mg provides a daily exposure of ganciclovir comparable to that of intravenous ganciclovir 5 mg/kg. A single, randomised, nonblind study indicated that oral valganciclovir (900mg twice daily for 3 weeks then 900 mg once daily) and intravenous ganciclovir (5 mg/kg twice daily for 3 weeks then 5 mg/kg once daily) were equally effective in the treatment of newly diagnosed CMV retinitis in 160 patients with AIDS. Valganciclovir appears to have a similar tolerability profile to intravenous ganciclovir during induction therapy in patients with AIDS and newly diagnosed CMV retinitis. During maintenance therapy with valganciclovir, the most commonly reported adverse events included neutropenia, anaemia, thrombocytopenia, gastrointestinal (including diarrhoea, nausea, vomiting and abdominal pain), fever, headache, insomnia, peripheral neuropathy, paraesthesia and retinal detachment.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Anemia; Antiviral Agents; Biological Availability; Cytomegalovirus Retinitis; Fever; Ganciclovir; Gastrointestinal Diseases; Headache; Humans; Infusions, Intravenous; Neutropenia; Paresthesia; Peripheral Nervous System Diseases; Prodrugs; Randomized Controlled Trials as Topic; Retinal Detachment; Sleep Initiation and Maintenance Disorders; Thrombocytopenia; Valganciclovir