Urinary excretion of ganciclovir contributes to improvement of adenovirus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation.

A nine-yr-old girl developed AdV-associated HC after bone marrow transplantation. Intravenous GCV markedly reduced urinary AdV DNA loads and improved clinical findings. This appeared to result partly from a high concentration of GCV in urine. GCV may be effective for AdV-induced HC without definitive disseminated infection.

Determination of ganciclovir in different matrices from solid organ transplanted patients treated with a wide range of concomitant drugs.

The aim of the present study was to develop a time-efficient chromatographic method for the analysis of therapeutic concentrations of ganciclovir (GCV) in plasma, urine as well as dialysate (from continuous renal replacement therapy) from solid organ transplant recipient treated with either GCV or its prodrug valganciclovir (VGCV) in combination with a wide variety of other concomitant drugs. Sample preparation was performed by reversed phase solid phase extraction and was followed by separation of the analytes on a reversed phase column using isocratic elution with a mobile phase consisting of acetonitrile-a counter ion (50 mM 1-heptanesulfonic acid) in an aqueous sodium dihydrogen phosphate buffer (pH 2.1; 10 mM) (10:90 v/v) and a fluorescence detector. Validation of the method showed linearity within the concentration range of 0.1-40 microg/mL for plasma and 0.1-120 microg/mL for urine and dialysate (R(2)>0.99, n> or =5). Accuracy and precision (evaluated at 0.1, 5 and 40 microg/mL) were both satisfactory. The LLOQ was determined to be 0.1 microg/mL. The method was successfully applied on clinical samples from renal transplant recipients treated with VGCV in combination with a variety of usually used concomitant drugs for solid organ transplant recipients.

Validation of microdialysis sampling for oral availability studies by means of a new ganciclovir prodrug.

Microdialysis sampling was validated for oral availability studies using ganciclovir (9-(1, 3-dihydroxy-2-propoxymethyl) guanine) and a ganciclovir prodrug (9-(1-L-valyloxy-3-octadecanoyloxy-prop-2-oxymethyl) guanine). Three different techniques were used in the study; microdialysis, blood and urinesampling. The oral uptake (11+/-2%) and the urinary recovery (106+/-5%) were determined. Animals given ganciclovir subcutaneously were subject either to microdialysis and blood sampling or to microdialysis alone. There was no significant difference between microdialysis and blood sampling in terms of blood concentration data, CL, Vd, half-life or AUC by means of Student's t-test. The oral bioavailability of the prodrug was 40+/-7% estimated from microdialysis sampling data and 48+/-4% estimated from urine sampling data. It is concluded that microdialysis is a valid method to use in pharmacokinetic studies of oral availability as well as for basic pharmacokinetic parameter estimation.

Simple reversed-phase high-performance liquid chromatography quantitation of ganciclovir in human serum and urine.

A fast, simple, and cost-effective HPLC method for the quantitation of the antiviral drug ganciclovir is described. The serum samples are extracted with perchloric acid and neutralized with potassium phosphate buffer, and urine samples are diluted with distilled water. A reversed-phase column with isocratic elution by 15 mM potassium phosphate buffer (pH 2.5) containing 0.25% acetonitrile is used to separate ganciclovir; quantitation is by UV absorbance at 254 nm. Total turnaround time is 22 min; more than 3000 samples can be run on a single column without loss of peak quality. The limit of quantitation is 0.05 micrograms/ml. Recoveries varied from 91 to 107% with coefficients of variation ranging from 0.387 to 7.95%.

A sensitive and specific liquid-chromatographic assay for determination of ganciclovir in plasma and urine and its application to pharmacokinetic studies in the rabbit.

A liquid-chromatographic assay for the analysis of ganciclovir in plasma and urine is described. This assay involves the use of acyclovir, an antiviral drug structurally related to ganciclovir, as the internal standard. A two-step sample preparation method is used. After protein is precipitated with acetonitrile and the addition of diethyl ether, ganciclovir and the internal standard are back extracted into a small volume of aqueous ammonium phosphate, taking advantage of their relatively high water solubility. This isocratic method is specific and sufficiently sensitive to allow quantification of ganciclovir throughout the entire range of concentrations observed during therapeutic use of this antiviral drug. There was no interference from various over-the-counter and prescription drugs often prescribed to patients most likely to receive ganciclovir therapy. This assay was used to analyze plasma and urine samples obtained after intravenous administration of ganciclovir to rabbits. Biexponential decay of ganciclovir plasma concentration-time and urinary excretion rate-time profiles was observed, with a mean distribution half-life of 15.8 min and an elimination half-life of 96 min. The mean renal clearance, 9.0 ml/min per kg, exceeds the glomerular filtration rate in the rabbit, indicating that ganciclovir is actively secreted in the renal tubule. Similar results were obtained by determining the renal clearance at steady state during constant-rate intravenous infusion of ganciclovir.