Pharmacokinetic Parameters of Innovative Valganciclovir Versus Generic Valganciclovir
Condition: Kidney Transplantation; Cytomegalovirus Infections; Pharmacokinetics; Therapeutic Equivalency
MeSH terms: Cytomegalovirus Infections
Study type: Interventional

Summary: 
      Cytomegalovirus (CMV) is the most common opportunistic viral pathogen in solid organ
      transplant receptors (SOTR). In Mexico, the experience using generic immunosuppressants have
      been demonstrated a wide variation in the pharmacokinetic parameters between generic and
      innovative formulation, resulting in a suboptimal absorption of the drug and reaching
      infratherapeutic trough levels in blood. In this study the investigators will compare the
      pharmacokinetic parameters of innovative and generic valganciclovir in renal transplant
      recipients.
    

Detailed description: 
      Cytomegalovirus (CMV) is the most common opportunistic viral pathogen in solid organ
      transplant receptors (SOTR). In the absence of prophylaxis, the frequency of CMV disease in
      high-risk recipients (R- / D +) is 60% and 20% for intermediate-risk patients (R + / D + or
      -). For universal prophylaxis, the antivirals most commonly used are valganciclovir (valGCV)
      and IV ganciclovir. ValGCV, a prodrug of ganciclovir, has a bioavailability of 60%, which
      represents more than 10 times that those obtained with ganciclovir.

      Pharmacokinetic studies of Valganciclovir in SOTR have been demonstrated that insufficient
      doses can diminish its clinical efficacy and the development of viral resistance, while
      excessive doses can increase its toxicity.

      The risk of viremia may be associated with ineffective plasma doses, as described by
      Wiltshire et al., where values of the area under the curve (AUC) between 40 and 50 μg/h/ml
      were associated with a lower incidence of viremia, while lower AUC values are associated with
      an increase 8 times more for viral replication rates. As a result, pharmacokinetic studies in
      SOTR guide the investigators in continuing with the research of their clinical impact.

      A generic drug before their release to the market needs to show that is bioequivalent with
      the innovative drug, assuming that it has the same therapeutic effects.

      The studies for demonstrate bioequivalence are carried out in controlled conditions with
      healthy participants, different of SOTR characteristics as: age, gender, race, comorbidities
      and concomitant medication. In addition, the excipients used in generic drug are different
      from those of the innovative drug, so the properties of the formulation can be modified
      (particle size or half-life), therefore, the efficacy and drug safety.

      The primary outcome will be compare the pharmacokinetic parameters of the innovative versus
      generic formulation of valGCV in renal transplant recipients.
    

Intervention name(s): Generic Valganciclovir; Innovative Valganciclovir
Intervention type(s): Drug; Drug
Intervention description(s): 900 mg daily during 4 days; 900 mg daily during 4 days
Other intervention name(s): Valganciclovir Pisa; Valcyte
Intervention MeSH terms: Valganciclovir
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Pharmacovigilance study, prospective, observational, analytical, single center, cross over design, with random assignment to the sequence of both formulations in the same patient. Our aim will be compare the pharmacokinetic parameters of the innovative versus generic formulation of valGCV in renal transplant recipients under valGCV prophylaxis in the early posttransplant stage.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: valganciclovir; kidney transplantation; pharmacokinetics