Concentrations Of Penciclovir Research Articles

Activity of penciclovir against Epstein-Barr virus.

Penciclovir inhibited the productive replication cycle of Epstein-Barr virus (EBV) in assays measuring infectious virus production, viral antigen expression, and viral DNA synthesis. In the test measuring inhibition of EBV DNA synthesis, 50% effective concentrations of penciclovir and acyclovir were 2.3 +/- 0.8 and 2.2 +/- 0.6 micrograms/ml, respectively. The 50% cell growth inhibitory concentration of penciclovir was > 100 micrograms/ml for both P3HR-1 and Raji cells. Penciclovir is a selective inhibitor of EBV in cell culture.

Pharmacokinetics of famciclovir in subjects with varying degrees of renal impairment

To characterize the pharmacokinetics of a single 500 mg oral dose of famciclovir in subjects with varying degrees of renal impairment. Twenty-seven subjects were enrolled in an open-label parallel-group study. Eighteen patients had renal impairment (average age [ +/- SD], 49 +/- 12 years), and nine subjects were healthy volunteers (average age, 28 +/- 7 years). Patients with renal impairment were stratified into groups based on estimated creatinine clearance (CLCR): mild impairment (CLCR, 60 to 80 ml/min/1.73 m2), moderate impairment (CLCR, 30 to 59 ml/min/1.73 m2) and severe impairment (CLCR, 5 to 29 ml/min/1.73 m2). Plasma and urine specimens were analyzed for concentrations of penciclovir, the antivirally active metabolite of famciclovir, by reverse-phase HPLC. Plasma data were analyzed with use of model-independent methods. In subjects with normal renal function (CLCR > 80), the mean maximum plasma concentrations of penciclovir was 2.83 micrograms/ml (range, 1.30 to 3.82 micrograms/ml) and the mean time to reach maximum concentration was 0.89 hours (range, 1/2 to 1 1/2 hours). The mean apparent terminal elimination half-life was 2.15 hours (range, 1.56 to 2.87 hours). A linear relationship was observed between the plasma elimination rate constant and CLCR and between renal clearance and CLCR. Mean area under the plasma concentration-time curve from zero to infinity was approximately tenfold higher and the plasma elimination rate constant was approximately fourfold lower in patients with severe renal impairment than in subjects with normal renal function. Consideration should be given to modification of the dosing schedule of famciclovir from the usual 8-hour interval to a 12-hour interval for patients with moderate renal impairment (CLCR 30 to 59 ml/min/1.73 m2) or a 24-hour interval for patients with severe renal impairment (CLCR < 30 ml/min/1.73 m2).

Pharmacokinetics of Famciclovir in Man

This review presents briefly the results of a number of studies conducted in healthy volunteers, designed to investigate the pharmacokinetics of famciclovir, the oral form of the antiviral compound, penciclovir. These studies have shown that famciclovir is absorbed rapidly and extensively following oral administration. Extensive pre-systemic metabolism of famciclovir occurs since compound-related material in plasma consists almost entirely of deacetylated and oxidized metabolites. Little or no parent compound is detected in plasma or urine. The major metabolite of famciclovir is penciclovir. Maximum plasma concentrations of penciclovir are achieved rapidly following oral administration of famciclovir, and total systemic availability of penciclovir is high (77%). Pharmacokinetic parameters for penciclovir are linear over the famciclovir oral dose range 125–750 mg and the penciclovir intravenous dose range 10–20 mg kg−1. The distribution of penciclovir after intravenous administration is consistent with loc...

The tolerance to and pharmacokinetics of penciclovir (BRL 39,123A), a novel antiherpes agent, administered by intravenous infusion to healthy subjects.

The tolerance to and pharmacokinetics of intravenously administered penciclovir (BRL 39,123A), a novel anti-herpes agent, were investigated in 15 healthy male subjects. The volunteers were divided into three groups, receiving either 10, 15 or 20 mg/kg penciclovir by a 60 min constant-rate infusion. Blood samples were taken sequentially up to 48 h after the start of the infusion and urine collections made at appropriate intervals up to 72 h. After a simple solid phase extraction, concentrations of penciclovir in plasma and urine were determined using HPLC with U.V. detection. Mean values of Cmax, corresponding usually with the end of infusion, and of AUC appeared to increase proportionately with dose. Furthermore, there was no evidence that dose significantly affected any individual pharmacokinetic parameter. Penciclovir was distributed into tissues with an overall mean volume of distribution of approximately 1.5 l.kg-1, i.e. approximately double that of body water. It was rapidly eliminated, with a mean total plasma clearance of 39.3 l.h-1, and a mean terminal-phase half-life of 2.0 h. The majority of the dose, approximately 70%, was excreted unchanged in the urine. Mean renal clearance of BRL 39,123 was 28.1 l.h-1, which exceeds normal glomerular filtration rate and approaches renal plasma flow. At all dose-levels, the infusions of penciclovir were well tolerated, with no evidence of drug-related adverse events.