Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytomegalovirus (CMV) infection is a major complication after allogeneic stem cell transplantation (SCT). Valganciclovir (V-GCV) is an oral prodrug hydrolyzed to the anti-CMV drug ganciclovir (GCV). A randomized, multicenter, crossover, open-label clinical trial compared exposure to GCV after V-GCV and intravenous GCV (IV-GCV) as preemptive therapy for CMV disease in SCT. The primary objective was to compare exposure to GCV in patients with CMV infection stratified for intestinal graft-versus-host disease (I-GVHD). Secondary objectives were the assessment of safety and efficacy. Patients without I-GVHD had a higher exposure to GCV after V-GCV when compared with IV-GCV (area under the concentration-time curve from drug administration to last observed concentration after 12 hours [AUC(0-12)] 53.8 +/- 17.97 microg/mL . h [mean +/- SD] vs 39.5 +/- 13.91; P < .001; ratio of V-GCV/IV-GCV was 1.4; 90% confidence interval [CI], 1.2-1.5). This was also true in patients with I-GVHD grades I-II (AUC(0-12) 52.9 +/- 21.75 vs 33.1 +/- 12.97 mug/mL . h; P = .018; ratio 1.6; 90% CI, 1.3-2.0). Absolute bioavailability of GCV after V-GCV was approximately 75% in individuals with or without I-GVHD grades I-II. No severe GCV-related toxicity was observed and efficacy and safety was comparable (84-day follow-up). This supports the use of V-GCV in SCT, even in patients with I-GVHD grades I-II. Due to higher exposure after V-GCV compared with IV-GCV, patients should be monitored carefully for safety reasons.
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PMID:Oral valganciclovir leads to higher exposure to ganciclovir than intravenous ganciclovir in patients following allogeneic stem cell transplantation. 1635 7

Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection continues to be an important cause of morbidity and mortality in the hematopoietic stem cell transplant (HSCT) recipient. The standard drug for pre-emptive therapy is intravenous ganciclovir (GCV). Valganciclovir (VGC), the oral pro-drug of GCV, has excellent bioavailability and is ideal for oral therapy. Since March 2002, VGC was adopted in our center for outpatient pre-emptive therapy in all patients undergoing allogeneic HSCT. Fifty-two allogeneic HSCT recipients were followed weekly via Digene hybrid capture assay. Patients with a positive assay were treated with VGC 900 mg p.o. b.i.d. x 14 days followed by 900 mg p.o. QD until at least 7 days after a negative test. Eighteen patients (14 sib, four MUD) had 30 episodes of CMV DNA detection treated with oral VGC. Median duration of therapy was 21 days (range 10-21 days). The rate of response was 93% (28/30) as confirmed by a negative assay within 14 days. No significant toxicity was encountered. Two patients failed oral VGC. One case of CMV enteritis was diagnosed in a patient with acute GVHD. Pre-emptive therapy of CMV infection with oral VGC is safe and effective in allogeneic HSCT recipients.
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PMID:Valganciclovir is safe and effective as pre-emptive therapy for CMV infection in allogeneic hematopoietic stem cell transplantation. 1653 16

The pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir were compared in allogeneic stem cell transplant recipients with stable graft-versus-host disease of the gastrointestinal tract. Twenty-two evaluable adult patients were randomized to receive a single dose of open-label study drug (900 mg of oral valganciclovir or 5 mg/kg of intravenous ganciclovir). After a washout period of 2 to 7 days, patients were crossed over to receive the alternate study drug. Ganciclovir and valganciclovir concentrations in plasma were measured over 24 hours after dosing. Noninferiority of 900 mg of valganciclovir relative to intravenous ganciclovir was concluded if the lower limit of the 1-sided 95% confidence interval of the ratio of least-square means of the ganciclovir area under the curve (AUC) for the 2 study drugs was >80%. Valganciclovir was found to be rapidly absorbed and converted into ganciclovir. The ganciclovir exposure after 900 mg of valganciclovir noninferior to that of intravenous ganciclovir (AUC0-infinity, 52.1 and 53.8 microg.h/mL, respectively; 95% confidence interval of the ratio of least square means of AUC0-infinity, 82.48%-118.02%). Oral valganciclovir could be a useful alternative to intravenous ganciclovir in certain stable stem cell transplant patients who require prophylaxis or preemptive therapy for cytomegalovirus infection.
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PMID:Pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir in allogeneic stem cell transplant patients with graft-versus-host disease of the gastrointestinal tract. 1673 36