ORAL GANCICLOVIR IN PEDIATRIC TRANSPLANT RECIPIENTS - A PHARMACOKINETIC STUDY

An oral formulation of ganciclovir (GAN) has been shown to be effectiv e as prophylaxis of cytomegalovirus (CMV) after liver transplantation in an adult population. There are no data on the use or dose of oral G AN in pediatric transplant recipients. We evaluated the pharmacokineti cs of oral GAN in a group of such patients. Nine patients (4 kidney an d 5 liver transplant recipients, age 0.9-13 yr) were treated with the commercial formulation of oral GAN after transplant. All patients were considered at risk for CMV disease based on the use of anti-lymphocyt e antibody (n=5), and/or the use of a CMV positive organ in a CMV nega tive recipient (n=5) or based on being a recipient of a liver transpla nt (n=4). They received oral GAN for 84 +/- 29 d. All recipients had n ormal renal function as estimated by the Schwartz formula. While on a stable dose of oral GAN for at least 4 d (mean +/- SD 8.4 +/- 7, range 4-27 d), l-ml serum samples were obtained before and at various times after dosing for the measurement of GAN levels. GAN levels were deter mined at a central laboratory by high-performance liquid chromatograph y. In 7 of the patients, a sufficient number of levels were obtained p ost-dosing to calculate the area under the curve using the linear trap ezoidal rule. C-min, the morning trough concentration, and C-min, the peak concentration, were determined by inspection. Doses of oral GAN w ere increased if C-min levels were less than 0.5-1.0 mu g/ml. Adequate levels of GAN were achieved in these patients at doses of 21.8-38.5 m g/kg or 568-990 mg/m(2) every 8 h. There was a better correlation betw een the maximum GAN blood concentration and body surface area (R-2=0.5 2, p= 0.008) than with body weight (R-2=0.36, p=0.04). Oral GAN was we ll tolerated in the 7 patients without evidence of leukopenia, thrombo cytopenia, or nephrotoxicity. No CMV disease occurred, although one pa tient had probable CMV syndrome with the development CMV IgM antibodie s. These data suggest that oral GAN may be safely administered to pedi atric transplant recipients. With normal renal function, the dosing sh ould be in the range 20-40 mg/kg or 500-700 mg/m(2) q 8 h. Further dat a in children with impaired renal function is required.