Evaluation of valaciclovir dosage reduction in continuous ambulatory peritoneal dialysis patients.

In continuous ambulatory peritoneal dialysis (CAPD) patients, acyclovir-induced neurotoxicity is reported to be associated with high serum drug levels even when following the recommended reduced doses for this renal failure population. In view of the high oral bioavailability of valaciclovir (the L-valyl ester of acyclovir) the risk of neurotoxicity becomes more prominent. The present study was conducted in 12 CAPD patients who were administered a single oral dose of 500 mg valaciclovir. Acyclovir was analyzed by high-performance liquid chromatography. Relative pharmacokinetic parameters were estimated based on acyclovir concentrations at 8, 12 and 24 h post-dose. High inter-patient variations were observed with acyclovir apparent total clearance 7.238 +/- 4 l/h and half-life (T1/2) 22.27 +/- 16.82 h. However, dosage simulations confirmed supratherapeutic acyclovir concentrations for all participants when following the recommended dose of 1,000 mg valaciclovir/24 h for varicella zoster infections.

Rapid determination of valaciclovir and acyclovir in human biological fluids by high-performance liquid chromatography using isocratic elution.

A rapid high-performance liquid chromatographic assay with isocratic elution is developed for the simultaneous quantification of valaciclovir (VACV) prodrug and its active converted compound, acyclovir (ACV), in biological fluids of treated patients. For serum, the samples are deproteinized with perchloric acid in presence of 1-methylguanosine as the internal standard (IS). For urine and dialysis liquid, the samples are diluted with a mobile phase containing the IS, then filtered. VACV, ACV and the IS are separated on a SymmetryShield RP-8 column with acetonitrile-ammonium phosphate buffer as the mobile phase and detected at 254 nm. The chromatographic time is about 12 min. The relative standard deviations (RSD) of VACV and ACV standards are between 0.5 and 3.5%. Most endogenous nucleosides and their metabolites, psychotropic drugs and drugs of abuse are shown not to interfere with this technique. The method has been applied to study the pharmacokinetics of VACV and ACV in serum, dialysis liquid and urine of renal failure patients on continuous ambulatory peritoneal dialysis (CAPD) under oral treatment of VACV.

Initiation of clinical pharmacy in Greece.

INTRO: There was neither Clinical Pharmacy practice in Greece nor Hospital Formularies. Clinical Pharmacy (CP) services started experimentally during a 3-month period (February 1995-April 1995) at the 2nd surgical Department of "Apostle Paul-KAT" Hospital in Athens. Since then there has been a strategy plan for further CP development. Our aim is to give information about these first steps in introducing CP in Greece. METHOD: The work at the Department was based on the prescription monitoring of every patient, realizing the prescribing trends and giving priority to certain prescribing problems. Eventually there was a focus on antibiotics and respiratory system drugs. RESULTS: 250 patients 91 interventions for alternative drug treatment and the duration of antibiotic treatment 25 interventions for individualization of drug dosage. 15 cases of monitoring adverse effects. 12 discussions with patients consulting them about their drug treatment 4 educational presentations. High acceptance by the medical staff. Comparison of 2 months (pre and post CP services) revealed 50.7% reduction in antibiotics and respiratory system drugs. Total cost saving 1,034120 drs-->E 2,787 for one month. CONCLUSIONS: The results of the 1st experimental 3-month period are indicative for the consequences of CP services both for the quality of pharmaceutical care and pharmaco-economics. Implementation of CP services by organizing a CP dept or Unit will influence the pharmaceutical policy of the Hospital and lead to institutional changes, such as a Hospital Formulary.

Clinical pharmacokinetics of oral acyclovir in patients on continuous ambulatory peritoneal dialysis.

It is increasingly recognised that dose adjustment of oral acyclovir in continuous ambulatory peritoneal dialysis (CAPD) patients is necessary to avoid neurotoxicity. A single 800-mg oral dose of acyclovir was administered to 10 uninfected anuric patients who were treated by CAPD. Serial blood and CAPD bag samples were analysed for acyclovir during the 31 h after dosing. Serum acyclovir levels were measured using radioimmunoassay and the pharmacokinetic parameters were estimated by linear regression using the STRIPE computer programme. Peak plasma levels of 8.95 +/- 3.95 microM were achieved at 4.1 +/- 1.85 h with the T1/2 calculated to be 14.52 +/- 3 h. The mean predicted serum acyclovir levels at steady state after 1,600-, 800- and 600-mg daily doses were 13.76, 6.88 and 5.16 microM, respectively. The present recommended daily doses of acyclovir (1,600 mg) for end-stage renal disease patients leads to supratherapeutic levels therefore increasing the risk and incidence of neurotoxicity. Computer modelling of various dosage simulations suggests that daily doses of 800 and 600 mg will achieve therapeutic levels (4-8 microM).