Clinical Pharmacokinetics

, Volume 48, Issue 6, pp 399–418 | Cite as

Valganciclovir in Adult Solid Organ Transplant Recipients

Pharmacokinetic and Pharmacodynamic Characteristics and Clinical Interpretation of Plasma Concentration Measurements
  • Nancy Perrottet
  • Laurent A. Decosterd
  • Pascal Meylan
  • Manuel Pascual
  • Jerome Biollaz
  • Thierry Buclin
Review Article


Valganciclovir and ganciclovir are widely used for the prevention of cytomegalovirus (CMV) infection in solid organ transplant recipients, with a major impact on patients’ morbidity and mortality. Oral valganciclovir, the ester prodrug of ganciclovir, has been developed to enhance the oral bioavailability of ganciclovir. It crosses the gastrointestinal barrier through peptide transporters and is then hydrolysed into ganciclovir. This review aims to describe the current knowledge of the pharmacokinetic and pharmacodynamic characteristics of this agent, and to address the issue of therapeutic drug monitoring.

Based on currently available literature, ganciclovir pharmacokinetics in adult solid organ transplant recipients receiving oral valganciclovir are characterized by bioavailability of 66±10% (mean ± SD), a maximum plasma concentration of 3.1 ± 0.8 mg/L after a dose of 450 mg and of 6.6 ± 1.9 mg/L after a dose of 900 mg, a time to reach the maximum plasma concentration of 3.0±1.0 hours, area under the plasma concentration-time curve values of 29.1±5.3mg · h/L and 51.9±18.3mg · h/L (after 450 mg and 900 mg, respectively), apparent clearance of 12.4 ± 3.8 L/h, an elimination half-life of 5.3 ± 1.5 hours and an apparent terminal volume of distribution of 101 ±36 L. The apparent clearance is highly correlated with renal function, hence the dosage needs to be adjusted in proportion to the glomerular filtration rate. Unexplained interpatient variability is limited (18% in apparent clearance and 28% in the apparent central volume of distribution). There is no indication of erratic or limited absorption in given subgroups of patients; however, this may be of concern in patients with severe malabsorption.

The in vitro pharmacodynamics of ganciclovir reveal a mean concentration producing 50% inhibition (IC50) among CMV clinical strains of 0.7 mg/L (range 0.2–1.9 mg/L). Systemic exposure of ganciclovir appears to be moderately correlated with clinical antiviral activity and haematotoxicity during CMV prophylaxis in high-risk transplant recipients. Low ganciclovir plasma concentrations have been associated with treatment failure and high concentrations with haematotoxicity and neurotoxicity, but no formal therapeutic or toxic ranges have been validated.

The pharmacokinetic parameters of ganciclovir after valganciclovir administration (bioavailability, apparent clearance and volume of distribution) are fairly predictable in adult transplant patients, with little interpatient variability beyond the effect of renal function and bodyweight. Thus ganciclovir exposure can probably be controlled with sufficient accuracy by thorough valganciclovir dosage adjustment according to patient characteristics. In addition, the therapeutic margin of ganciclovir is loosely defined. The usefulness of systematic therapeutic drug monitoring in adult transplant patients therefore appears questionable; however, studies are still needed to extend knowledge to particular subgroups of patients or dosage regimens.


Ganciclovir Valganciclovir Solid Organ Transplant Recipient Oral Ganciclovir Intravenous Ganciclovir 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Support for this work was partly provided by internal funds and partly by an unrestricted research grant from Roche (Basel, Switzerland) for studies related to transplantation. The funding source had no role in the analysis and reporting of data, nor in the decision to submit the manuscript for publication. The authors have no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007; 357: 2601–14PubMedCrossRefGoogle Scholar
  2. 2.
    Lowance D, Neumayer H-H, Legendre CM, et al., for the International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. N Engl J Med 1999; 340: 1462–9PubMedCrossRefGoogle Scholar
  3. 3.
    Preiksaitis JK, Brennan DC, Fishman J, et al. Canadian Society of Transplantation consensus workshop on cytomegalovirus management in solid organ transplant: final report. Am J Transplant 2005; 5: 218–27PubMedCrossRefGoogle Scholar
  4. 4.
    Hodson E, Craig J, Strippoli G, et al. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev 2008; (16): CD003774Google Scholar
  5. 5.
    Paya C, Humar A, Dominguez E, et al. Efficacy and safety of valganciclovir vs oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 2004; 4: 611–20PubMedCrossRefGoogle Scholar
  6. 6.
    Sugawara M, Huang W, Fei YJ, et al. Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J Pharm Sci 2000; 89: 781–9PubMedCrossRefGoogle Scholar
  7. 7.
    Insook K, Xian-Yan C, Seonyoung K, et al. Identification of a human valacyclovirase. J Biochem 2003; 278: 25348–56Google Scholar
  8. 8.
    Lai L, Xu Z, Zhou J, et al. Molecular basis of prodrug activation by human valacyclovirase, an α-amino acid ester hydrolase. J Biol Chem 2008; 283: 9318–27PubMedCrossRefGoogle Scholar
  9. 9.
    Scott JC, Partovi N, Ensom MHH. Ganciclovir in solid organ transplant recipients: is there a role for clinical pharmacokinetic monitoring?. Ther Drug Monit 2004; 26: 68–77PubMedCrossRefGoogle Scholar
  10. 10.
    Pescovitz MD, Rabkin J, Merion RM, et al. Valganciclovir results in improved oral absorption of ganciclovir in liver transplant recipients. Antimicrob Agents Chemother 2000; 44: 2811–5PubMedCrossRefGoogle Scholar
  11. 11.
    Chamberlain CE, Penzak SR, Alfaro RM, et al. Pharmacokinetics of low and maintenance dose of valganciclovir in kidney transplant recipients. Am J Transplant 2008; 8: 1297–302PubMedCrossRefGoogle Scholar
  12. 12.
    Pescovitz MD, Jain A, Robson A, et al. Establishing pharmacokinetics bioequivalence of valganciclovir oral solution versus the tablet formulation. Transplant Proc 2007; 39: 3111–6PubMedCrossRefGoogle Scholar
  13. 13.
    Wiltshire H, Hirankarn S, Farrell C, et al., the Valganciclovir Solid Organ Transplant Study Group. Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients. Clin Pharmacokinet 2005; 44: 495–507PubMedCrossRefGoogle Scholar
  14. 14.
    Armendariz Y, Caldes A, Colom H, et al. Population pharmacokinetics of valganciclovir in solid organ transplant recipients infected by cytomegalovirus [abstract no. 1012]. 15th Meeting, Population Approach Group in Europe; 2006 Jun 14–16; Bruges [online]. Available from URL: [Accessed 2009 Jun 23]Google Scholar
  15. 15.
    Winston DJ, Baden LR, Gabriel DA, et al. Pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir in allogeneic stem cell transplant patients with graft-versus-host disease of the gastrointestinal tract. Biol Blood Marrow Transplantation 2006; 12: 635–40CrossRefGoogle Scholar
  16. 16.
    Einsele H, Reusser P, Bornhauser M, et al. Oral valganciclovir leads to higher exposure to ganciclovir than intravenous ganciclovir in patients following allogeneic stem cell transplantation. Blood 2006; 107: 3002–8PubMedCrossRefGoogle Scholar
  17. 17.
    Jung D, Dorr A. Single-dose pharmacokinetics of valganciclovir in HIV- and CMV-seropositive subjects. J Clin Pharmacol 1999; 39: 800–4PubMedCrossRefGoogle Scholar
  18. 18.
    Brown F, Banken L, Saywell K, et al. Pharmacokinetics of valganciclovir and ganciclovir following multiple oral dosages of valganciclovir in HIV- and CMV-seropositive volunteers. Clin Pharmacokinet 1999; 37: 167–76PubMedCrossRefGoogle Scholar
  19. 19.
    Martin DF, Sierra-Madero J, Walmsley S, et al. A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis. N Engl J Med 2002; 346: 1119–26PubMedCrossRefGoogle Scholar
  20. 20.
    Czock D, Scholle C, Rasche FM, et al. Pharmacokinetics of valganciclovir and ganciclovir in renal impairment. Clin Pharmacol Ther 2002; 72: 142–50PubMedCrossRefGoogle Scholar
  21. 21.
    Pescovitz MD, Pruett TL, Gonwa T, et al. Oral ganciclovir dosing in transplant recipients and dialysis patients based on renal function. Transplantation 1998; 66: 1104–7PubMedCrossRefGoogle Scholar
  22. 22.
    Wolfe EJ, Mathur V, Tomlanovich S, et al. Pharmacokinetics of mycophenolate mofetil and intravenous ganciclovir alone and in combination in renal transplant recipients. Pharmacotherapy 1997; 17: 591–8PubMedGoogle Scholar
  23. 23.
    Rondeau E, Farquet C, Fries D, et al. Treatment of cytomegalovirus infections with ganciclovir in kidney transplant recipients: clinical and pharmacokinetic study. Presse Med 1991; 20: 2030–2PubMedGoogle Scholar
  24. 24.
    Tornatore KM, Garey KW, Saigal N, et al. Ganciclovir pharmacokinetics and cytokine dynamics in renal transplant recipients with cytomegalovirus infection. Clin Transplant 2001; 15: 297–308PubMedCrossRefGoogle Scholar
  25. 25.
    Campos F, Pou L, Pascual C. Serum monitoring of ganciclovir [abstract]. Ther Drug Monit 1993; 15: 156CrossRefGoogle Scholar
  26. 26.
    Boeckh M, Zaia JA, Jung D, et al. A study of the pharmacokinetics, antiviral activity, and tolerability of oral ganciclovir for CMV prophylaxis in marrow transplantation. Biol Blood Marrow Transplantation 1998; 4: 13–9CrossRefGoogle Scholar
  27. 27.
    Shepp DH, Dandliker PS, de Miranda P, et al. Activity of 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine in the treatment of cytomegalovirus pneumonia. Ann Intern Med 1985; 103: 368–73PubMedGoogle Scholar
  28. 28.
    Fletcher C, Sawchuk R, Chinnock B, et al. Human pharmacokinetics of the antiviral drug DHPG. Clin Pharmacol Ther 1986; 40: 281–6PubMedCrossRefGoogle Scholar
  29. 29.
    Anderson RD, Griffy KG, Jung D, et al. Ganciclovir absolute bioavailability and steady-state pharmacokinetics after oral administration of two 3000-mg/d dosing regimens in human immunodeficiency virus- and cytomegalo-virus-seropositive patients. Clin Ther 1995; 17: 425–32PubMedCrossRefGoogle Scholar
  30. 30.
    Jung D, Griffy K, Wong R, et al. Absolute bioavailability and dose proportionality of oral ganciclovir after ascending multiple doses in human immunodeficiency virus (HIV)-positive patients. J Clin Pharmacol 1998; 38: 1122–8PubMedGoogle Scholar
  31. 31.
    Lalezari JP, Friedberg DN, Bissett J, et al., Roche Cooperative Oral Ganciclovir Study Group. High dose oral ganciclovir treatment for cytomegalovirus retinitis. J Clin Virol 2002; 24: 67–77PubMedCrossRefGoogle Scholar
  32. 32.
    Hochster H, Dieterich D, Bozzette S, et al. Toxicity of combined ganciclovir and zidovudine for cytomegalovirus disease associated with AIDS: an AIDS Clinical Trials Group study. Ann Intern Med 1990; 113: 111–7PubMedGoogle Scholar
  33. 33.
    Piketty C, Bardin C, Gilquin J, et al. Low plasma concentrations achieved with conventional schedules of administration of ganciclovir in patients with AIDS. J Infect Dis 1996; 174: 188–90PubMedCrossRefGoogle Scholar
  34. 34.
    Laskin OL, Stahl-Bayliss CM, Kalman CM, et al. Use of ganciclovir to treat serious cytomegalovirus infections in patients with AIDS. J Infect Dis 1987; 155: 323–7PubMedCrossRefGoogle Scholar
  35. 35.
    Laskin OL, Cederberg DM, Mills J, et al. Ganciclovir for the treatment and suppression of serious infections caused by cytomegalovirus. Am J Med 1987; 83: 201–7PubMedCrossRefGoogle Scholar
  36. 36.
    Aweeka FT, Gambertoglio JG, Kramer F, et al. Foscarnet and ganciclovir pharmacokinetics during concomitant or alternating maintenance therapy for AIDS-related cytomegalovirus retinitis. Clin Pharmacol Ther 1995; 57: 403–12PubMedCrossRefGoogle Scholar
  37. 37.
    Jacobson MA, de Miranda P, Cederberg DM, et al. Human pharmacokinetics and tolerance of oral ganciclovir. Antimicrob Agents Chemother 1987; 31: 1251–4PubMedCrossRefGoogle Scholar
  38. 38.
    Winston DJ, Ho WG, Bartoni K, et al. Ganciclovir therapy for cytomegalovirus infections in recipients of bone marrow transplants and other immunosuppressed patients. Rev Infect Dis 1988; 10 Suppl. 3: 547–53CrossRefGoogle Scholar
  39. 39.
    Erice A, Jordan MC, Chace BA, et al. Ganciclovir treatment of cytomegalovirus disease in transplant recipients and others immunocompromised hosts. JAMA 1987; 22: 3082–7CrossRefGoogle Scholar
  40. 40.
    Weller S, Liao SHT, Cederberg DM, et al. The pharmacokinetics of ganciclovir in patients with cytomegalovirus (CMV) infections [abstract]. J Pharm Sci 1987; 76 Suppl.: 120SGoogle Scholar
  41. 41.
    Asano-Mori Y, Kanda Y, Oshima K, et al. Pharmacokinetics of ganciclovir in haematopoietic stem cell transplantation recipients with or without renal impairment. J Antimicrob Chemother 2006; 57: 1004–7PubMedCrossRefGoogle Scholar
  42. 42.
    Sommadossi JP, Bevan R, Ling T, et al. Clinical pharmacokinetics of ganciclovir in patients with normal and impaired renal function. Rev Infect Dis 1988; 10 Suppl. 3: 507–14CrossRefGoogle Scholar
  43. 43.
    Bastien O, Boulieu R, Bleyzac N, et al. Ganciclovir use during mild renal failure in heart transplantation. Transplant Proc 1996; 28: 2876–7PubMedGoogle Scholar
  44. 44.
    McGavin JK, Goa KL. Ganciclovir: an update of its use in the prevention of cytomegalovirus infection and disease in transplant recipients. Drugs 2001; 61: 1153–83PubMedCrossRefGoogle Scholar
  45. 45.
    Perrottet N, Robatel C, Melyan P, et al. Disposition of valganciclovir during continuous renal replacement therapy in two lung transplant recipients. J Antimicrob Chemother 2008; 61: 1332–5PubMedCrossRefGoogle Scholar
  46. 46.
    Yuen GJ, Drusano GL, Fletcher C, et al. Population differences in ganciclovir clearance as determined by nonlinear mixed-effects modelling. J Antimicrob Chemother 1995; 39: 2350–2CrossRefGoogle Scholar
  47. 47.
    Preston SL, Drusano GL. Nonparametric expectation maximization population modeling of ganciclovir. J Clin Pharmacol 1996; 36: 301–10PubMedGoogle Scholar
  48. 48.
    Cimoch PJ, Lavelle J, Pollard R, et al. Pharmacokinetics of oral ganciclovir alone and in combination with zidovudine, didanosine, and probenecid in HIV-infected subjects. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 17: 227–34PubMedCrossRefGoogle Scholar
  49. 49.
    Jung D, AbdelHameed MH, Hunter J, et al. The pharmacokinetics and safety profile of oral ganciclovir in combination with trimethoprim in HIV- and CMV-seropositive patients. Br J Clin Pharmacol 1999; 47: 255–9PubMedCrossRefGoogle Scholar
  50. 50.
    Jung D, Griffy K, Dorr A, et al. Effect of high-dose oral ganciclovir on didanosine disposition in human immunodeficiency virus (HIV)-positive patients. J Clin Pharmacol 1998; 38: 1057–62PubMedCrossRefGoogle Scholar
  51. 51.
    Jung D, AbdelHameed MH, Teitelbaum P, et al. The pharmacokinetics and safety profile of oral ganciclovir combined with zalcitabine or stavudine in asymptomatic HIV- and CMV-seropositive patients. J Clin Pharmacol 1999; 39: 505–12PubMedGoogle Scholar
  52. 52.
    Cantarovich M, Latter D. Effect of prophylactic ganciclovir on renal function and cyclosporine levels after heart transplantation. Transpl Proceed 1994; 26: 2747–8Google Scholar
  53. 53.
    Mahony WB, Domin BA, Zimmerman TP. Ganciclovir permeation of human erythrocyte membrane. Pharmacology 1991; 41: 263–71Google Scholar
  54. 54.
    Li F, Maag H, Alfredson T. Prodrugs of nucleoside analogues for improved oral absorption and tissue targeting. J Pharm Sci 2008; 97: 119–34CrossRefGoogle Scholar
  55. 55.
    Cvestković RS, Wellington K. Valganciclovir: a review of its use in the management of CMV infection and disease in immunocompromised patients. Drugs 2005; 65: 859–78CrossRefGoogle Scholar
  56. 56.
    Matthews T, Boehme R. Antiviral activity and mechanism of action of ganciclovir. Rev Infect Dis 1988; 10 Suppl. 3: S490–4PubMedCrossRefGoogle Scholar
  57. 57.
    Smee DF, Martin J, Verheyden JPH, et al. Anti-herpesvirus activity of the acyclic nucleoside 9-(1, 3-dihydroxy-2-propoxymethyl) guanine. Antimicrob Agents Chemother 1983; 23: 676–82PubMedCrossRefGoogle Scholar
  58. 58.
    Tolman RL, Field AK, Karkas JD, et al. 2′-nor-cGMP: a seco-cyclic nucleotide with powerful anti-DNA-viral activity. Biochem Biophys Res Commun 1985; 128: 1329–35Google Scholar
  59. 59.
    Field AK, Davies ME, DeWitt C, et al. 9-[2-hydroxy-1-(hydroxymethyl)ethoxy]methylguanine: a selective inhibitor of herpes group virus replication. Proc Natl Acad Sci USA 1983; 80: 4139–43Google Scholar
  60. 60.
    Duke AE, Smee DF, Chernow M, et al. In vitro and in vivo activities of phosphate derivates of 9-(1,3-dihydroxy-2-propoxymethyl)-guanine against cytomegalovirus. Antiviral Res 1986; 6: 299–308PubMedCrossRefGoogle Scholar
  61. 61.
    Biron KK, Stanat SC, Sorrell JB, et al. Metabolic activation of the nucleoside analog 9-[2-hydroxy-1-(hydroxymethyl)ethoxy]methylguanine in human diploid fibroblasts infected with human cytomegalovirus. Proc Natl Acad Sci USA 1985; 82: 2473–7PubMedCrossRefGoogle Scholar
  62. 62.
    Freitas VR, Smee DF, Chernow M, et al. Activity of 9-(1,3-dihydroxy-2-propoxymethyl)-guanine compared with that of acyclovir against human, monkey, and rodent cytomegalovirus. Antimicrob Agents Chemother 1985; 28: 240–5PubMedCrossRefGoogle Scholar
  63. 63.
    Tocci Mj, Livelli TJ, Perry HC, et al. Effects of the nucleoside analog 2′-nor-2′-deoxyguanosine on the human cytomegalovirus replication. Antimicrob Agents Chemother 1984; 25: 247–52PubMedCrossRefGoogle Scholar
  64. 64.
    Plotkin AS, Drew WL, Felsenstein D, et al. Sensitivity of clinical isolates of human cytomegalovirus to 9-(1,3-dihydroxy-2-propoxymethyl) guanine. J Infect Dis 41985; 152: 833–4PubMedCrossRefGoogle Scholar
  65. 65.
    Felstein D, D’Amico DJ, Hirsch MS, et al. Treatment of cytomegalovoris retinitis with 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine. Ann Intern Med 1985; 103: 377–80Google Scholar
  66. 66.
    Taylor DL, Jeffries DJ, Taylor-Robinson D, et al. The susceptibility of adenovirus infection to anticytomegalovirus drug, ganciclovir (DHPG). FEMS Microbiol Lett 1988; 49: 337–41CrossRefGoogle Scholar
  67. 67.
    Biron KK, Fyfe JA, Stanat SC, et al. A human cytomegalovirus mutant resistant to the nucleoside analog 9-[2-hydroxy-1-(hydroxymethyl)ethoxy]methyguanine (BW B759U) induces reduced level of BW B759U triphosphate. Proc Natl Acad Sci USA 1986; 83: 8769–73PubMedCrossRefGoogle Scholar
  68. 68.
    Rush J, Mills J. Effect of combinations of dihydrofluoromethylornithine (DFMO) and 9[1,3-dihydroxy-2-propoxy) methyl]guanine (DHPG) on human cytomegalovirus. J Med Virol 1987; 21: 269–87PubMedCrossRefGoogle Scholar
  69. 69.
    Shepp DH, Dandliker PS, de Miranda P, et al. Activity of 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine in the treatment of cytomegalovirus pneumonia. Ann Intern Med 1985; 10: 368–73Google Scholar
  70. 70.
    Cole NL, Balfour Jr HH. In vitro susceptibility of cytomegalovirus isolates from immunocompromised patients to acyclovir and ganciclovir. Diag Microbiol Infect Dis 1987; 6: 255–61CrossRefGoogle Scholar
  71. 71.
    Drew WL, Miner R, Saleh E. Antiviral susceptibility testing of cytomegalo-virus criteria for detecting resistance to antivirals. Clin Diagn Virol 1993; 1: 179–85PubMedCrossRefGoogle Scholar
  72. 72.
    Mar EC, Cheng YC, Huang ES, et al. Effect of 9-(1,3-dihydroxy-2-propoxymethyl)-guanine on human cytomegalovirus replication in vitro. Antimicrob Agents Chemother 1983; 24: 518–27PubMedCrossRefGoogle Scholar
  73. 73.
    Cheng YC, Huan ES, Lin JC, et al. Unique spectrum of activity of 9-(1,3-dihydroxy-2-propoxymethyl)-guanine against herpesviruses in vitro and its mode of action against herpes simplex virus type 1. Proc Natl Acad Sci USA 1983; 80: 2767–70PubMedCrossRefGoogle Scholar
  74. 74.
    McSharry JJ, McDonough A, Olson B, et al. Susceptibilites of human cytomegalovirus clinical isolates to BAY38-4766, BAY43-9695, and ganciclovir. Antimicrob Agents Chemother 2001; 45: 2925–7PubMedCrossRefGoogle Scholar
  75. 75.
    Boivin G, Erice A, Crane DD, et al. Ganciclovir susceptibilities of cytomegalovirus (CMV) isolates from solid organ transplant recipients with CMV viremia after antiviral prophylaxis. J Infect Dis 1993; 168: 332–5PubMedCrossRefGoogle Scholar
  76. 76.
    Slavin MA, Bindra RR, Gleaves CA, et al. Ganciclovir sensitivity of cytomegalovirus at diagnosis and during treatment of cytomegalovirus pneumonia in marrow transplant recipients. Antimicrob Agents Chemother 1993; 37: 1360–3PubMedCrossRefGoogle Scholar
  77. 77.
    Fishman JA, Doran MT, Volpicelli SA, et al. Dosing of intravenous ganciclovir for the prophylaxis and treatment of cytomegalovirus infection in solid organ transplant recipients. Transplantation 2000; 69: 389–94PubMedCrossRefGoogle Scholar
  78. 78.
    Matthews T, Boehme R. Antiviral activity and mechanism of action of ganciclovir. Rev Infect Dis 1988; 8 (3Suppl.): 490–4SCrossRefGoogle Scholar
  79. 79.
    Boivin G, Goyette N, Gilbert C, et al. Absence of cytomegalovirus-resistance mutations after valganciclovir prophylaxis, in a prospective multicenter study of solid-organ transplant recipients. J Infect Dis 2007; 189: 1615–8CrossRefGoogle Scholar
  80. 80.
    Boivin G, Goyette N, Gilbert C, et al. Analysis of cytomegalovirus DNA polymerase (UL54) mutations in solid organ transplant patients receiving valganciclovir or ganciclovir prophylaxis. J Med Virol 2005; 77: 425–9PubMedCrossRefGoogle Scholar
  81. 81.
    Wiltshire H, Paya C, Pescovitz M, et al., the Valganciclovir Solid Organ Transplant Study Group. Pharmacodynamics of oral ganciclovir and valganciclovir in solid organ transplant recipients. Transplantation 2005; 79: 1477–83PubMedCrossRefGoogle Scholar
  82. 82.
    Gruber SA, Garnick J, Morawski K, et al. Cytomegalovirus prophylaxis with valganciclovir in African-American renal allograft recipients based on donor/recipient serostatus. Clin Transplant 2005; 19: 273–8PubMedCrossRefGoogle Scholar
  83. 83.
    Spector SA, Busch DF, Follansbee S, et al. Pharmacokinetic, safety, and antiviral profiles of oral ganciclovir in persons infected with human immunodeficiency virus: a phase I/II study. AIDS Clinical Trials Group and Cytomegalovirus Cooperative Study Group. J Infect Dis 1995; 171: 1431–7PubMedCrossRefGoogle Scholar
  84. 84.
    Pescovitz MD, Brook B, Jindal RM, et al. Oral ganciclovir in pediatric transplant recipients: a pharmacokinetic study. Clinical Transplant 1997; 11: 613–7Google Scholar
  85. 85.
    Filler G, Lampe D, von Bredow MA, et al. Prophylactic oral ganciclovir after renal transplantation-dosing and pharmacokinetics. Pediatr Nephrol 1998; 12: 6–9PubMedCrossRefGoogle Scholar
  86. 86.
    Piketty C, Bardin C, Gilquin J, et al. Monitoring plasma levels of ganciclovir in AIDS patients receiving oral ganciclovir as maintenance therapy for CMV retinitis. Clin Microbiol Infect 2000; 6: 117–20PubMedCrossRefGoogle Scholar
  87. 87.
    Zhang D, Lapeyraque AL, Popon M, et al. Pharmacokinetics of ganciclovir in pediatric renal transplant recipients. Pediatr Nephrol 2003; 18: 943–8PubMedCrossRefGoogle Scholar
  88. 88.
    Kimberlin DW, Acosta EP, Sanchez PJ, et al. Pharmacokinetics and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease. J Infect Dis 2008; 197: 836–45PubMedCrossRefGoogle Scholar
  89. 89.
    Sommadossi JP, Carlisle R. Toxicity of 3′-azido-3′-deoxythymidine and 9-(1,3-dihydroxy-2-propoxymethyl) guanine for normal human hematopoietic progenitor cells in vitro. Antimicrob Agents Chemother 1987; 31: 452–4PubMedCrossRefGoogle Scholar
  90. 90.
    Chamberlain SD, Biron KK, Dornsife RE, et al. An enantiospecific synthesis of the human cytomegalovirus antiviral agent [(R)-3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydoxybutyl]phosphoric acid. J Med Chem 1994; 37: 1371–7PubMedCrossRefGoogle Scholar
  91. 91.
    Kanda Y, Mineishi S, Saito T, et al. Pre-emptive therapy against cytomegalovirus (CMV) disease guided by CMV antigenemia assay after allogenic hematopoietic stem cell transplantation: a single-center experience in Japan. Bone Marrow Transplant 2001; 27: 437–44PubMedCrossRefGoogle Scholar
  92. 92.
    Salzberg B, Bowden RA, Hackman RC, et al. Neutrpenia in allogeneic marrow transplant recipients receiving ganciclovir for prevention of cytomegalovirus disease: risk factors and outcome. Blood 1997; 90: 2502–8Google Scholar
  93. 93.
    Buhles Jr W, Mastre BJ, Tinker AJ, et al. Ganciclovir treatment of life- or sight-threatening cytomegalovirus infections: experience in 314 immunocompromised patients. Rev Infect Dis 1988; 10 Suppl. 3: 495–503CrossRefGoogle Scholar
  94. 94.
    Manuel O, Venetz JP, Fellay J, et al. Efficacy and safety of universal valganciclovir prophylaxis combined with a tacrolimus/mycophenolate-based regimen in kidney transplantation. Swiss Med Wkly 2007; 137: 669–76PubMedGoogle Scholar
  95. 95.
    Combarnous F, Fouque D, Chossegros P, et al. Neurologic side-effects of ganciclovir. Clin Nephrol 1994; 42: 279–80PubMedGoogle Scholar
  96. 96.
    Peyrière H, Jeziorrsky E, Jalabert A, et al. Neurotoxicity related to valganciclovir in a child with impaired renal function: usefulness of therapeutic drug monitoring. Ann Pharmacother 2006; 40: 143–6PubMedGoogle Scholar
  97. 97.
    Chen JL, Brocavich JM, Lin AYF. Psychiatric disturbances associated with ganciclovir therapy. Ann Pharmacother 1992; 26: 193–5PubMedGoogle Scholar
  98. 98.
    Hansen BA, Greenberg KS, Richter JA. Ganciclovir-induced psychosis. N Engl J Med 1996; 31: 1397CrossRefGoogle Scholar
  99. 99.
    Barton TL, Roush MK, Dever LL. Seizures associated with ganciclovir therapy. Pharmacotherapy 1992; 12: 413–5PubMedGoogle Scholar
  100. 100.
    Sharthkumar A, Shaw PJ. Ganciclovir-induced encephalopathy in a bone marrow transplant recipient. Bone Marrow Transplant 1999; 24: 421–3CrossRefGoogle Scholar
  101. 101.
    Davis CL, Springmeyer S, Gmerek BJ, et al. Central nervous system side effects of ganciclovir. N Engl J Med 1990; 29: 933–4Google Scholar
  102. 102.
    Figge HL, Baille GR, Briceland LL, et al. Possible ganciclovir-induced hepatotoxicity in patients with AIDS. Clin Pharm 1992; 11: 432–4PubMedGoogle Scholar
  103. 103.
    Shea BF, Hoffman S, Sesin GP, et al. Ganciclovir hepatotoxicity. Pharmacotherapy 1987; 7: 223–6PubMedGoogle Scholar
  104. 104.
    Ensom MHH, Davis GA, Cropp CD, et al. Clinical pharmacokinetics in the 21st century. Clin Pharmacokinet 1998; 34: 265–79PubMedCrossRefGoogle Scholar
  105. 105.
    Singh N, Wannstedt C, Keyes L, et al. Efficacy of valganciclovir administered as preemptive therapy for cytomegalovirus disease in liver transplant recipients: impact on viral load and late-onset cytomegalovirus. Transplantation 2005; 79: 85–90PubMedCrossRefGoogle Scholar
  106. 106.
    Singh N, Wannstedt C, Keyes L, et al. Valganciclovir as preemptive therapy for cytomegalovirus in cytomegalovirus-seronegative liver transplant recipients of cytomegalovirus-seropositive donor allografts. Liver Transpl 2008; 14: 240–4PubMedCrossRefGoogle Scholar
  107. 107.
    Babel N, Gabdrakhmanovy L, Juergensen JS, et al. Treatment of cytomegalovirus disease with valganciclovir in renal transplant recipients: a single center experience. Transplantation 2004; 78: 283–5PubMedCrossRefGoogle Scholar
  108. 108.
    Lopau K, Greser A, Wanner C. Efficacy and safety of preemptive anti-CMV therapy with valganciclovir after kidney transplantation. Clin Transplant 2007; 21: 80–5PubMedCrossRefGoogle Scholar
  109. 109.
    Devyatko E, Zuckermann A, Ruzicka M, et al. Pre-emptive treatment with oral valganciclovir in management of CMV infection after cardiac transplantation. J Heart Lung Transplant 2004; 23: 1277–82PubMedCrossRefGoogle Scholar
  110. 110.
    Aigher C, Jaksch P, Winkler G, et al. Initial experience with oral valganciclovir for pre-emptive cytomegalovirus therapy after lung transplantation. Wien Klin Wochenschr 2005; 117: 480–4CrossRefGoogle Scholar
  111. 111.
    Fellay J, Venetz JP, Aubert D, et al. Treatment of cytomegalovirus infection or disease in solid organ transplant recipients with valganciclovir. Am J Transplant 2005; 5: 1781–2PubMedCrossRefGoogle Scholar
  112. 112.
    Díaz-Pedroche C, Lumbreras C, San Juan R, et al. Valganciclovir preemptive therapy for the prevention of cytomegalovirus disease in high-risk seropositive solid-organ transplant recipients. Transplantation 2006; 82: 30–5PubMedCrossRefGoogle Scholar
  113. 113.
    Len O, Gavaldà J, Aguado JM, et al. Valganciclovir as treatment for cytomegalovirus disease in solid organ transplant recipients. Clin Infect Dis 2008; 46: 20–7PubMedCrossRefGoogle Scholar
  114. 114.
    Humar A, Siegal D, Moussa G, et al. A prospective assessment of valganciclovir for the treatment of cytomegalovirus infection and disease in transplant recipients. J Infect Dis 2005; 192: 1154–7PubMedCrossRefGoogle Scholar
  115. 115.
    Åsberg A, Humar A, Rollag H, et al., on behalf of the VICTOR Study Group. Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 2007; 7: 2106–3PubMedCrossRefGoogle Scholar
  116. 116.
    Perrottet N, Beguin A, Meylan P, et al. Determination of aciclovir and ganciclovir in human plasma by liquid chromatography: spectrofluorimetric detection and stability studies in blood samples. J Chromatogr B Analyt Technol Biomed Life Sci 2007; 852: 420–9PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  • Nancy Perrottet
    • 1
  • Laurent A. Decosterd
    • 1
  • Pascal Meylan
    • 2
  • Manuel Pascual
    • 3
  • Jerome Biollaz
    • 1
  • Thierry Buclin
    • 1
  1. 1.Division of Clinical Pharmacology and ToxicologyUniversity HospitalLausanneSwitzerland
  2. 2.Microbiology InstituteUniversity HospitalLausanneSwitzerland
  3. 3.Organ Transplantation CenterUniversity HospitalLausanneSwitzerland

Personalised recommendations