Low Plasma Concentrations Achieved with Conventional Schedules of Administration of Ganciclovir in Patients with AIDS

Abstract

Plasma concentration of ganciclovir was studied prospectively in 15 AIDS patients treated for acute cytomegalovirus (CMV) retinitis. Ganciclovir was administered at a mean dose of 10.3 +/- 0.6 mg/kg/day. The mean trough plasma concentration was 0.6 +/- 0.3 mg/L (n = 24), and the mean peak concentration was 7.2 +/- 2.4 mg/L (n = 6). In 12 patients, trough concentrations were below the range that has been associated with effective treatment. Low trough concentrations were associated with treatment failure in 6 patients. Following an increase in the daily dose, improvement was observed in 4 of the 6 patients. These results suggest that low plasma ganciclovir levels are associated with the failure of therapy. Monitoring the plasma concentration of ganciclovir may thus be useful before considering the virus to be resistant to the drug or before switching from ganciclovir to foscarnet.

The targeting of primary effusion lymphoma cells for apoptosis by inducing lytic replication of human herpesvirus 8 while blocking virus production

“…Pharmacokinetic studies of valproate, PFA, and ganciclovir demonstrate that concentrations that were effective in this study can be safely achieved in patients. 40,75,76 This suggests that combined treatment with valproate and antiviral agents could selectively target tumors that are infected with HHV-8 for destruction without killing noninfected cells. Either PFA or ganciclovir should prevent valproate-induced production of HHV-8 without preventing apoptosis, and this should limit any long-term problems associated with virus dissemination or paracrine responses to viral proteins such as vIL-6 that are expressed early in the lytic cascade.…”

Monitoring of Trough Plasma Ganciclovir Levels and Peripheral Blood Cytomegalovirus (CMV)-Specific CD8 + T Cells To Predict CMV DNAemia Clearance in Preemptively Treated Allogeneic Stem Cell Transplant Recipients

“…Since intracellular GCV triphosphate is the active form of this compound, the plasma GCV concentration is simply a surrogate of the drug's antiviral activity (1,2). Monitoring trough plasma GCV levels in AIDS patients receiving oral GCV as maintenance therapy for CMV retinitis was shown to be clinically useful in predicting therapy failure and disease progression (4,5). Nevertheless, no therapeutic concentrations of GCV have been formally defined (6).…”

“…In fact, the therapeutic range of plasma GCV concentrations has not been formally established in any clinical setting, although trough levels between 0.2 and 2.0 mg/liter in solid organ transplant recipients with CMV end-organ disease and Ͼ0.6 mg/liter in HIV patients with retinitis have been tentatively proposed (4)(5)(6)15). In this context, we found that maintained trough plasma GCV levels of Ͼ0.6 mg/liter were not consistently associated with CMV DNAemia clearance.…”

Diagnosis and Management of Infectious Esophagitis Associated with Human Immunodeficiency Virus Infection

“…65 Secondary prophylaxis with intravenous ganciclovir or foscarnet did not affect disease progression among HIV-infected patients with gastrointestinal CMV disease. 66 Primary prophylaxis against HSV disease is not currently recommended. Patients with frequent relapses of genital, oropharyngeal, or esophageal disease usually benefit from secondary prophylaxis with acyclovir (400 to 600 mg daily).…”