Lack of interaction between valaciclovir, the L-valyl ester of aciclovir, and digoxin.
OBJECTIVE
Changes in both digoxin and aciclovir renal clearance following coadministration with some other renally eliminated drugs have been reported. The potential interaction of valaciclovir, with its antiherpetic metabolite aciclovir, and digoxin was investigated.


METHODS
Twelve healthy volunteers (seven males, five females) participated in an open, randomized, four-period crossover study. Valaciclovir, 1000 mg, was given alone on one occasion, and on another, after the second of two 0.75 mg digoxin doses administered 12 h apart. Blood samples and all urine were collected up to 12 h following the valaciclovir dose for aciclovir radioimmunoassay. On a third occasion, digoxin was given alone and on a fourth, with 1000 mg valaciclovir three times/day for 8 days starting 12 h before the first digoxin dose. Blood samples were taken up to 168 h and all urine collected up to 24 h following the second dose for digoxin radioimmunoassay.


RESULTS
There were no clinically significant differences in digoxin or aciclovir pharmacokinetic parameters when digoxin or valaciclovir was given alone or in combination.


CONCLUSIONS
No dosage adjustment is required when valaciclovir and digoxin are coadministered.
Soul-Lawton
J H
JH
Glaxo Wellcome Research and Development, Greenford, Middlesex, UK.
Weatherley
B C
BC
Posner
J
J
Layton
G
G
Peck
R W
RW
D000212:Acyclovir / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004077:Digoxin / Q000009:adverse effects / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D011355:Prodrugs / Q000009:adverse effects / Q000493:pharmacokinetics*; D000077483:Valacyclovir; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D000998:Antiviral Agents; D002316:Cardiotonic Agents; D011355:Prodrugs; D004077:Digoxin; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir