Pharmacokinetics of mycophenolate mofetil and intravenous ganciclovir alone and in combination in renal transplant recipients.

STUDY OBJECTIVES

To evaluate the pharmacokinetics of mycophenolic acid and its glucuronide metabolite alone and in the presence of ganciclovir, and to determine the pharmacokinetics of ganciclovir alone and in combination with mycophenolate mofetil.

DESIGN

Randomized, open-label, three-way crossover study.

PATIENTS

Twelve kidney transplant recipients.

INTERVENTIONS

Mycophenolate mofetil 1500 mg orally and ganciclovir 5 mg/kg intravenously were each given alone and in combination with at least a 1-week washout period between treatment arms.

MEASUREMENTS AND MAIN RESULTS

Blood samples were obtained to measure mycophenolic acid and ganciclovir by high-performance liquid chromatography. Mean (+/-SD) oral plasma clearance for mycophenolic acid alone and with ganciclovir was 3.11 +/- 0.72 and 3.19 +/- 0.72 ml/min/kg (p = 0.64). The overall disposition of the major metabolite, MPA-glucuronide, was unchanged, with approximately 70% of the administered dose eliminated as the glucuronide conjugate for both arms of the study. Mean genciclovir serum clearance was 1.80 +/- 0.58 ml/min/kg for ganciclovir and 1.70 +/- 0.55 ml/min/kg for ganciclovir plus mycophenolate mofetil (p = 0.11; 10 patients). Renal clearance of ganciclovir was decreased when the drugs were administered in combination, 1.43 +/- 0.54 (ganciclovir) and 1.26 +/- 0.44 (both drugs) ml/min/kg (p = 0.02; 10 patients).

CONCLUSION

The single-dose pharmacokinetics of mycophenolic acid and its glucuronide metabolite were unchanged by the addition of ganciclovir. Total serum clearance of ganciclovir was unchanged by the addition of mycophenolate mofetil, however, renal clearance was slightly decreased.