title: Liquid chromatographic method for the determination of ganciclovir and/or acyclovir in human plasma using pulsed amperometric detection.
abstract: We have developed a simple, rapid and highly sensitive method for determining plasma concentrations of ganciclovir and/or acyclovir by using reversed-phase chromatography followed by pulsed amperometric detection. A linear relationship between the amount of ganciclovir (0.05-10 microg/ml plasma) or acyclovir (0.1-20 microg/ml plasma) and peak height ratio was obtained. The relative standard deviations of all standard curves were greater than or equal to 0.999. The limits of detection for ganciclovir and acyclovir quantitation were 10 ng/ml and 50 ng/ml (signal/noise >3), respectively. Daily fluctuations of plasma standard curves (n=5) for the ganciclovir and acyclovir samples were small, with relative standard deviations (RSD) of 3.3 and 4.5% (n=5), respectively. The intra-assay precision for the ganciclovir and acyclovir samples were 6.9 (n=5) and 5.5% (n=5), respectively. Inter-assay precision of ganciclovir (n=3) and acyclovir (n=3) ranged from 2.6 to 6.8% and 3.5 to 5.0%, respectively. Using this method, the pharmacokinetics and removal of ganciclovir during continuous hemodiafiltration (CHDF) in a liver transplant recipient being treated for severe cytomegalovirus infection was investigated. The mean (+/-SD) ratio of ganciclovir concentrations at the inlet and outlet of the dialyzer (C(outlet)/C(inlet)) was 0.56+/-0.09. The areas under the curves of ganciclovir up to 12 h postdosing (AUC(0-->12)) at the inlet and outlet of the dialyzer were 12.54 microg h/ml and 7.16 microg h/ml, respectively. The ultrafiltrate of ganciclovir was 16.6 mg. The terminal elimination half-life (T(1/2)) of ganciclovir during CHDF was 3.6 h. These results demonstrate that CHDF effectively removes ganciclovir. Until formal guidelines have been established, ganciclovir or acyclovir dosage should be adjusted according to the results of monitoring of plasma drug concentration. The method described here is suitable for clinical monitoring of plasma ganciclovir or acyclovir levels in solid organ transplant recipients and for use in studies involving pharmacokinetics.
authors.affiliation: Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo, 060-8648, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kishino
authors.forename: Yoh
authors.initials: Y
authors.lastname: Takekuma
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sugawara
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shimamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Furukawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Todo
authors.forename: Katsumi
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D000212:Acyclovir / Q000097:blood* / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004563:Electrochemistry / Q000379:methods*; D015774:Ganciclovir / Q000097:blood* / Q000493:pharmacokinetics; D006440:Hemofiltration; D006801:Humans; D016031:Liver Transplantation; D012015:Reference Standards; D012680:Sensitivity and Specificity
chemical_list: D000998:Antiviral Agents; D015774:Ganciclovir; D000212:Acyclovir