93021
document
Oral ganciclovir dosing in transplant recipients and dialysis patients based on renal function . BACKGROUND An oral formulation of ganciclovir ( GCV ) was recently approved for the prevention of cytomegalovirus disease in solid organ transplant recipients . This study was designed to determine the bioavailability of GCV and to test a dosing algorithm in transplant and dialysis patients with different levels of renal function . METHODS Pharmacokinetic studies were carried out in 23 patients who were either a recipient of an organ transplant or on hemodialysis . Drug dosing was established by the following algorithm based on calculated creatinine clearance ( CrCl ) : CrCl = [ ( 140-age ) x body weight ] / ( 72 x Cr ) x 0.85 for women that is , CrCl > 50 ml/min , 1000 mg every 8 hr ; CrCl of 25-50 ml/min , 1000 mg every 24 hr ; CrCl of 10-24 ml/ min , 500 mg every day ; CrCl < 10 ml/min ( or on dialysis ) , 500 mg every other day after dialysis . GCV was taken within 30 min after a meal . The patients received oral GCV for between 12 days and 14 weeks . Serum specimens ( or plasma from patients on hemodialysis ) obtained at steady state were analyzed for GCV concentrations by high-performance liquid chromatography . In nine of the transplant recipients , absolute bioavailability was determined by comparing GCV levels after single oral and intravenous doses of GCV . RESULTS The following GCV concentrations ( mean +/-SD ) were determined : with CrCl of > or =70 ml/min , the minimum steady-state concentration ( Cmin ) and maximum concentration ( Cmax ) were 0.78+/-0.46 microg/ml and 1.42+/-0.37 microg/ml , respectively , with a 24-hr area under the concentration time curve ( AUC0-24 ) of 24.7+/-7.8 microg x hr/ml ; with CrCl of 50-69 ml/min , the Cmin and Cmax were 1.93+/-0.48 and 2.57+/-0.39 microg/ml , respectively , with an AUC0-24 of 52.1+/-10.1 microg x hr/ml ; with CrCl of 25-50 ml/min , the Cmin and Cmax were 0.41+/-0.27 and 1.17+/-0.32 microg/ml , respectively , with an AUC0-24 of 14.6+/-7.4 microg x hr/ml . For one patient with a CrCl of 23.8 ml/min , the Cmin and Cmax were 0.32 and 0.7 microg/ml , respectively , with an AUC0-24 of 10.7 microg x hr/ml . With CrCl of < 10 ml/min , the mean Cmin and Cmax were 0.75+/-0.42 and 1.59+/-0.55 microg/ml , respectively , with a mean AUC0-24 of 64.6+/-18.8 microg x hr/ml . Absolute bioavailability , for the nine patients so analyzed , was 7.2+/-2.4 % . For those patients with end-stage renal failure , GCV concentrations fell during dialysis from a mean of 1.47+/-0.48 microg/ml before dialysis to 0.69+/-0.38 microg/ml after dialysis . CONCLUSIONS The bioavailability of oral GCV in transplant patients was similar to that observed in human immunodeficiency virus-infected patients . However , levels between 0.5 and 1 microg/ml ( within the IC50 of most cytomegalovirus isolates ) could be achieved with tolerable oral doses . The proposed dosing algorithm resulted in adequate levels for patients with CrCl greater than 50 ml/min and for patients on dialysis . For patients with CrCl between 10 and 50 ml/min , the levels achieved were low and these patients would likely benefit from increased doses .
93022
Intervention_Pharmacological
GCV
93023
Intervention_Pharmacological
GCV was taken within 30 min after a meal
93024
Intervention_Pharmacological
oral GCV
93025
Intervention_Pharmacological
oral GCV
93026
Outcome_Physical
Serum specimens ( or plasma from patients on hemodialysis
93027
Outcome_Other
absolute bioavailability
93028
Outcome_Physical
GCV levels
93029
Outcome_Physical
GCV concentrations
93030
Outcome_Physical
Absolute bioavailability
93031
Outcome_Physical
GCV concentrations
93032
Participant_Sample-size
23 patients
93033
Participant_Condition
end-stage renal failure
93034
Participant_Condition
human immunodeficiency virus-infected