Population Pharmacokinetics of Ganciclovir in Solid-Organ Transplant Recipients Receiving Oral Valganciclovir

Perrottet, Nancy; Csajka, Chantal; Pascual, Manuel; Manuel, Oriol; Lamoth, Frédéric; Meylan, Pascal; Aubert, John‐David; Venetz, J.-P.; Soccal, Paola M.; Décosterd, Laurent A.; Biollaz, J; Buclin, Thierry

doi:10.1128/aac.00836-08

Cited by 45 publications

(86 citation statements)

References 31 publications

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“…In general, however, such regimens do not reliably assure adequate systemic ganciclovir exposure. 21,[33][34][35] A theoretic argument for low-dose valganciclovir is that it may lessen toxicity, 36 but we noted that dose reduction was followed shortly by discontinuation of valganciclovir in each patient. The 17% toxicity rate was within the 7.5% to 32% range previously reported for lung transplant recipients receiving valganciclovir prophylaxis, 23,24 a significant finding because alemtuzumab has potential myelosuppressive effects.…”

Section: Discussionmentioning

confidence: 94%

Cytomegalovirus disease among donor-positive/recipient-negative lung transplant recipients in the era of valganciclovir prophylaxis

Mitsani

Nguyen

Kwak

et al. 2010

The Journal of Heart and Lung Transplantation

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Section: Discussionmentioning

confidence: 94%

Cytomegalovirus disease among donor-positive/recipient-negative lung transplant recipients in the era of valganciclovir prophylaxis

Mitsani

Nguyen

Kwak

et al. 2010

The Journal of Heart and Lung Transplantation

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“…RBV is thought to decrease in plasma possibly because of progressive uptake into red blood cells, a phenomenon that is reduced but not prevented at 4°C. A similar phenomenon has been previously observed for ganciclovir, another nucleotide antiviral (38,39). In patient samples, however, the equilibrium between RBV levels in plasma and red blood cells is already attained; therefore, red blood cell hemolysis must be avoided to prevent a spurious increase in RBV levels in plasma because of its release from lysed red blood cells.…”

Section: Discussionmentioning

confidence: 87%

Multiplex Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Therapeutic Drug Monitoring of Ribavirin, Boceprevir, and Telaprevir

Aouri

Moradpour

Cavassini

et al. 2013

Antimicrob Agents Chemother

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g New directly acting antivirals (DAAs) that inhibit hepatitis C virus (HCV) replication are increasingly used for the treatment of chronic hepatitis C. A marked pharmacokinetic variability and a high potential for drug-drug interactions between DAAs and numerous drug classes have been identified. In addition, ribavirin (RBV), commonly associated with hemolytic anemia, often requires dose adjustment, advocating for therapeutic drug monitoring (TDM) in patients under combined antiviral therapy. However, an assay for the simultaneous analysis of RBV and DAAs constitutes an analytical challenge because of the large differences in polarity among these drugs, ranging from hydrophilic (RBV) to highly lipophilic (telaprevir [TVR]). Moreover, TVR is characterized by erratic behavior on standard octadecyl-based reversed-phase column chromatography and must be separated from VRT-127394, its inactive C-21 epimer metabolite. We have developed a convenient assay employing simple plasma protein precipitation, followed by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of levels of RBV, boceprevir, and TVR, as well as its metabolite VRT-127394, in plasma. This new, simple, rapid, and robust HPLC-MS/MS assay offers an efficient method of real-time TDM aimed at maximizing efficacy while minimizing the toxicity of antiviral therapy.

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“…12,13) Perrottet et al reported a correlation between estimates of the area under the ganciclovir concentration-time curve (AUC) and the occurrence of leukopenia. 14) Kanda et al also showed that the total amount of ganciclovir and possibly the duration of high-dose ganciclovir may affect the incidence of neutropenia. 15) Furthermore, the predicted incidences of neutropenia of 15% and 20% were associated with AUC of 39 and 61 µg·h/mL, respectively.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Ganciclovir-Induced Thrombocytopenia and Leukopenia

Matsumoto

Shigemi

Ikawa

et al. 2015

Biological & Pharmaceutical Bulletin

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Ganciclovir is a nucleoside guanosine analogue that exhibits therapeutic activity against human cytomegalovirus infection, and is primarily excreted via glomerular filtration and active tubular secretion. The adverse effects induced by ganciclovir therapy are generally of a hematological nature and include thrombocytopenia and leukopenia. Low marrow cellularity and elevated serum creatinine have been identified as risk factors for ganciclovir-induced neutropenia. However, the risk factors for thrombocytopenia have yet to be determined. Therefore, this study investigated patients administered ganciclovir to determine the risk factors for thrombocytopenia and leukopenia. Thrombocytopenia occurred in 41 of these patients (30.6%). Multivariate logistic regression analysis identified three independent risk factors for thrombocytopenia: cancer chemotherapy (odds ratio (OR) 3.1), creatinine clearance (<20 mL/min) (OR 12.8), and the ganciclovir dose (≥12 mg/kg/d) (OR 15.1). Leukopenia occurred in 36 patients (28.6%), and white blood cell count (<6000 cells/mm 3 ) (OR 3.7) and the ganciclovir dose (≥12 mg/kg/d) (OR 7.8) were identified as risk factors. These results demonstrated that several factors influenced the occurrence of ganciclovir-induced thrombocytopenia and leukopenia, and suggest that special attention should be paid to patients receiving cancer chemotherapy with a low creatinine clearance (<20 mL/min) and high dose (≥12 mg/kg/d) in order to avoid ganciclovir-induced thrombocytopenia.

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Population Pharmacokinetics of Ganciclovir in Solid-Organ Transplant Recipients Receiving Oral Valganciclovir

Cited by 45 publications

References 31 publications

Cytomegalovirus disease among donor-positive/recipient-negative lung transplant recipients in the era of valganciclovir prophylaxis

Cytomegalovirus disease among donor-positive/recipient-negative lung transplant recipients in the era of valganciclovir prophylaxis

Multiplex Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Therapeutic Drug Monitoring of Ribavirin, Boceprevir, and Telaprevir

Risk Factors for Ganciclovir-Induced Thrombocytopenia and Leukopenia

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