valacyclovir and Hypertension

A randomized, double-blind study was conducted to evaluate the safety and pharmacokinetics of acyclovir following multiple-dose oral administration of valaciclovir (three times a day for 8 days) in geriatric volunteers (65 to 83 years of age). Pharmacokinetic evaluation was performed for three groups: normotensive subjects given 500-mg doses of valaciclovir (n = 11), normotensive subjects given, 1,000-mg doses of valaciclovir (n = 9), and thiazide diuretic-treated hypertensive subjects given 500-mg doses of valaciclovir (n = 9). Valaciclovir, the l-valyl ester of acylclovir, was rapidly absorbed and converted to acyclovir, with plasma valaciclovir concentrations generally undetectable or < or = 0.4 microgram/ml. The peak concentration of drug in plasma (Cmax) for acyclovir occurred at 1 to 2 h, and the half-life of acyclovir was 3 to 4 h in all three elderly groups. The Cmax and area under the concentration-time curve from 0 h to infinity (AUC0-infinity) values of acyclovir obtained on days 1 and 8 indicated no unexpected accumulation at steady state. The steady-state acyclovir Cmax (4.30 and 5.98 micrograms/ml) and daily AUC0-infinity (44 and 74 h.micrograms/ml) following dosing of valaciclovir (500 and 1,000 mg) three times a day were two to three times greater than those expected after high-dose oral acyclovir treatment (800 mg, five times daily). There were no valaciclovir-related changes or abnormalities in safety parameters and no reports of serious adverse experiences in these elderly volunteers. The plasma acyclovir concentration-time curves for the hypertensive and normotensive (500-mg valaciclovir treatment) elderly groups were almost superimposable, and acyclovir pharmacokinetic parameters for the two groups were not significantly different, indicating that concomitant thiazide diuretics do not alter acyclovir pharmacokinetics following valaciclovir dosing in the elderly. Compared with historical data for younger volunteers (creatinine clearance [CLCR] > 75 ml/min/1.73 m2), the elderly subjects (CLCR = 40 to 65 ml/min/1.73 m2) showed higher (approximately 15 to 20%) mean Cmaxs and higher (approximately 30 to 50%) mean AUC(0-infinity)s of acyclovir (P < 0.01), which were consistent with age-related decreases in CLCR. The increased acyclovir exposure from valaciclovir dosing will permit reduced dosing frequency and may result in improved efficacy in the management of herpesvirus diseases.

Topics: Acyclovir; Aged; Aged, 80 and over; Antiviral Agents; Diuretics; Double-Blind Method; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Prodrugs; Valacyclovir; Valine

A 97-year-old lady was hospitalized for left leg cellulitis. Comorbidity included hypertension and congestive heart failure. While in hospital, she developed a painless vesicular rash localized to the territory of the left trigeminal nerve (third branch), which evolved to pustules and crusts (Figure 1). A chickenpox-like disseminated eruption of vesicles followed within 4 days, with the same evolution pattern (Figure 2).The diagnosis of disseminated zoster was suspected. A PCR analysis confirmed the presence of varicella-zoster-virus (VZV) in an abdominal vesicle. The patient was treated with oral valacyclovir for 7 days. Clinical examination, laboratory tests (including HIV serology), and a chest radiograph revealed no evidence of underlying immunodeficiency or malignancy.

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Back; Face; Female; Heart Failure; Herpes Zoster; Herpesvirus 3, Human; Humans; Hypertension; Polymerase Chain Reaction; Valacyclovir; Valine

Topics: Acyclovir; Aged; Aged, 80 and over; Antiviral Agents; Brain Diseases, Metabolic; Diabetes Complications; Diagnosis, Differential; Herpes Zoster; Humans; Hypertension; Male; Myoclonus; Renal Dialysis; Renal Insufficiency; Valacyclovir; Valine