Evaluation of Pharmacokinetic Interactions After Oral Administration of Mycophenolate Mofetil and Valaciclovir or Aciclovir to Healthy Subjects

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• 作者：Dr Fran?ois Gimenez (1)
  Estelle Foeillet (1)
  Olivier Bourdon (1)
  Steve Weller (2)
  Christophe Garret (3)
  Roselyne Bidault (3)
  Eric Singlas (1)
  
• 刊名：Clinical Pharmacokinetics
• 出版年：2004
• 出版时间：August 2004
• 年：2004
• 卷：43
• 期：10
• 页码：685-692
• 全文大小：132KB
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• 作者单位：Dr Fran?ois Gimenez (1)
  Estelle Foeillet (1)
  Olivier Bourdon (1)
  Steve Weller (2)
  Christophe Garret (3)
  Roselyne Bidault (3)
  Eric Singlas (1)
  
  1. Pharmacie Clinique, H?pital Necker-Enfants Malades, 149 rue de Sévres, 75743, Paris, Cedex 15, France
  2. GlaxoSmithKline Inc., Research Triangle Park, North Carolina, USA
  3. GlaxoSmithKline, Marly-Le-Roi, France
  
• ISSN：1179-1926

文摘

Objective To investigate a potential pharmacokinetic interaction between mycophenolate mofetil (MMF) and aciclovir or valaciclovir. Study design and participants Fifteen healthy subjects were enrolled in a prospective, randomised, open-label, single-dose, cross-over study conducted at a single centre. Subjects received each of the following five oral treatments: (i) aciclovir 800mg alone; (ii) valaciclovir 2g alone; (iii) MMF 1g alone; (iv) valaciclovir 2g + MMF 1g; and (v) aciclovir 800mg + MMF 1g. The following pharmacokinetic parameters were estimated for aciclovir, mycophenolic acid (MPA) and its inactive glucuronide metabolite (MPAG) from the plasma concentration-time data using noncompartmental methods: area under the concentration-time curve from zero to infinity (AUC?, terminal elimination half-life (t?z), peak concentration (Cmax) and time to Cmax (tmax). The renal clearance (CLR) of aciclovir was also calculated. These parameters were compared when aciclovir or valaciclovir were coadministered with MMF relative to aciclovir, valaciclovir or MMF given alone. Results and discussion Aciclovir Cmax, tmax and AUC?were significantly increased by 40%, 0.38 hour and 31%, respectively, following coadministration of aciclovir and MMF, whereas aciclovir t?z was significantly decreased by 11%. Following coadministration of valaciclovir and MMF, aciclovir pharmacokinetic parameters were not significantly modified except for tmax (about 0.5 hour shorter with MMF). MPA and MPAG pharmacokinetic parameters were not significantly modified following coadministration of MMF with valaciclovir or aciclovir except for MPAG AUC? which was decreased by 12% with valaciclovir. Our results are similar to those reported in the literature, except for MPAG AUC. In urine, following coadministration of aciclovir and MMF, aciclovir CLR was significantly decreased by 19%. Competition between MPAG and aciclovir for renal tubular secretion could partly explain this phenomenon. Following coadmin-istration of valaciclovir and MMF, aciclovir CLR was not significantly modified. Conclusion In healthy subjects, interactions are observed after coadministration of MMF and aciclovir, but the extent of the interactions is unlikely to be of clinical significance. These interactions should be investigated in patients with abnormal renal function.