Contribution of Population Pharmacokinetics to Dose Optimization of Ganciclovir-Valganciclovir in Solid-Organ Transplant Patients

Antimicrobial Agents and Chemotherapy
A PadullésNúria Lloberas

Abstract

Treatment of solid-organ transplant (SOT) patients with ganciclovir (GCV)-valganciclovir (VGCV) according to the manufacturer's recommendations may result in over- or underexposure. Bayesian prediction based on a population pharmacokinetics model may optimize GCV-VGCV dosing, achieving the area under the curve (AUC) therapeutic target. We conducted a two-arm, randomized, open-label, 40% superiority trial in adult SOT patients receiving GCV-VGCV as prophylaxis or treatment of cytomegalovirus infection. Group A was treated according to the manufacturer's recommendations. For group B, the dosing was adjusted based on target exposures using a Bayesian prediction model (NONMEM). Fifty-three patients were recruited (27 in group A and 26 in group B). About 88.6% of patients in group B and 22.2% in group A reached target AUC, achieving the 40% superiority margin (P< 0.001; 95% confidence interval [CI] difference, 47 to 86%). The time to reach target AUC was significantly longer in group A than in group B (55.9 ± 8.2 versus 15.8 ± 2.3 days,P< 0.001). A shorter time to viral clearance was observed in group B than in group A (12.5 versus 17.6 days;P= 0.125). The incidences of relapse (group A, 66.67%, and group B, 9.01%) and late-onset in...Continue Reading

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Citations

May 26, 2017·Current Opinion in Infectious Diseases·Elizabeth RobilottiStan Deresinski
Mar 30, 2018·Transplantation·Camille N KottonUNKNOWN The Transplantation Society International CMV Consensus Group
May 10, 2020·Intensive Care Medicine·Mohd H Abdul-AzizUNKNOWN Infections in the ICU and Sepsis Working Group of International Society of Antimicrobial Chemotherapy (ISAC)
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Feb 5, 2021·Clinical Pharmacology and Therapeutics·Kevin J Downes, Jennifer L Goldman
Jul 14, 2021·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Kris OreschakChristina L Aquilante
Jul 3, 2021·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Miranda SoShahid Husain
May 31, 2019·Current Opinion in Organ Transplantation·Jonathan Hand, Gopi Patel
Oct 2, 2021·Clinical Pharmacology and Therapeutics·Bénédicte FranckJean-Baptiste Woillard

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