Acyclovir pharmacokinetics

Peritoneal Dialyis There is no information specific to administration of VALTREX in patients receiving peritoneal dialysis. The effect of chronic ambulatory peritoneal dialysis (CARD) and continuous arteriovenous hemofiltration/dialysis (CAVHD) on acyclovir pharmacokinetics has been studied. The removal of acyclovir after CARD and CAVHD is less pronounced than with hemodialysis, and the pharmacokinetic parameters closely resemble those observed in patients with ESRD not receiving hemodialysis. Therefore, supplemental doses of VALTREX should not be required following CARD or CAVHD. 

First-pass conversion of a prodrug to an active drug has been studied in pregnancy with the drug valacyclovir (71). Orally administered valacyclovir produced three times higher plasma levels of acyclovir than when acyclovir was administered orally. How ever/ the levels achieved with valacyclovir were somewhat lower than the reported levels in normal volunteers. On the other hand/ acyclovir pharmacokinetics were/ overall/ similar to what has been reported in nonpregnant womeiT. 

BG Petty, RI Whitty, S Liao, HC Krasny, LE Rocco, LG Davis, PS Lietman. Pharmacokinetics and tolerance of desciclovir, a prodrug of acyclovir, in healthy human volunteers. Antimicrob Agents Chemother 31 1317-1322, 1987. 

Weller, S., Blum, M. R., Doucette, M., Burnette, T., Cederberg, D. M., de Miranda, P., Smiley, M. L., Pharmacokinetics of the acyclovir prodrug valaciclovir after escalating single- and multiple-dose administration to normal volunteers, Clin. Pharmacol. Ther. 1993, 54, 595-605. 

P. de Miranda, T. C. Burnette, Metabolic Fate and Pharmacokinetics of the Acyclovir Prodrug Valaciclovir in Cynomolgus Monkeys , Drug Metab. Dispos. 1994, 22, 55-59. 

Mechanism of Action Avirustatic antiviral that is converted to acyclovir triphosphate, becoming part of the viral DNA chain. Therapeutic Effect Interferes with DNA synthesis and replication of herpes simplex virus and varicella-zoster virus. Pharmacokinetics Rapidly absorbed after PO administration. Protein binding 13%-18%. Rapidly converted by hydrolysis to the active compound acyclovir. Widely distributed to tissues and body fluids (including cerebrospinal fluid CSF ). Primarily eliminated in urine. Removed by hemodialysis. Half-life 2.5-3.3 hr (increased in impaired renal function). 

It is the L-valyl ester of acyclovir and rapidly converted into acyclovir after oral admnistration. Its mechanism of action and pharmacokinetics are similar to acyclovir. 

Drug interactions In a randomized, double-blind study, Zenapax or placebo was added to an immunosuppressive regimen of cyclosporine, mycophenolate mofetil, and steroids to assess tolerability, pharmacokinetics, and drug interactions. The addition of Zenapax did not result in an increased incidence of adverse events or a change in the types of adverse events reported. The following medications have been administered in clinical trials with Zenapax with no incremental increase in adverse reactions cyclosporine, mycophenolate mofetil, ganciclovir, acyclovir, azathioprine, and corticosteroids. 

Laskin OL, de Miranda P, King DH, et al. Effects of probenecid on the pharmacokinetics and elimination of acyclovir in humans. Antimicrob Agents Chemother 1982 21 804-807. 

Further, the enhanced transport of the P-gp substrate acyclovir across excised rat intestinal mucosa and Caco-2 monolayers in the presence of thiolated chitosan was found to be due to efflux pump inhibition (Palmberger et al. 2008). Co-administration of paclitaxel and thiolated polycarbophil significantly improved paclitaxel plasma levels and led to a more constant pharmacokinetic profile and reduced tumour growth in mammary cancer-induced rats (Foger et al. 2008). 

Pharmacokinetics Administration can be by an intravenous, oral, or topical route. The efficacy of topical applications is doubtful. The drug distributes well throughout the body, including the cerebrospinal fluid. Acyclovir is partially metabolized to an inactive product. Excretion into the urine occurs both by glomerular filtration and tubular secretion. Acyclovir accumulates in patients with renal failure. 

Kimberlin DF, Weller S, Whitley RJ, Andrews WW, Hauth JC, Lakeman F et al. Pharmacokinetics of oral valacyclovir and acyclovir in late pregnancy. Am J Obstet Gynecol 1998 179 846-51. 

Tu J, Wang L, Yang J, et al. Formulation and pharmacokinetics studies of acyclovir controlled-release capsules. Drug Dev Ind Pharm 2001 27(7) 687-692. 

Tod, M., Lokiec, F., Bidault, R., De Bony, F., Petitjean, O., and Aujard, Y. Pharmacokinetics of oral acyclovir in neonates and in infants A population analysis. Antimicrobial Agents and Chemotherapy 2001 45 150-157. 

Probenecid but not cidofovir alters zidovudine pharmacokinetics such that zidovudine doses should be reduced when probenecid is present, as should the doses of drugs similarly affected by probenecid fe.g., /i-lactam antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], acyclovir, lorazepam, furosemide, methotrexate, theophylline, and rifampin). Concurrent nephrotoxic agents are contraindicated, and an interval of 1 week before beginning cidofovir treatment is recommended after prior exposure to aminoglycosides, intravenous pentamidine, amphotericin foscamet, NSAIDs, or contrast dye. Cidofovir and oral ganciclovir in combination are poorly tolerated at full doses. 

Pharmacokinetics Acyclovir can be administered by the topical, oral, and intravenous routes. Renal excretion is the major route of elimination of acyclovir and dosage should be reduced in patients with renal impairment. 

Brigden D, Bye A, Fowle AS, et al. Human pharmacokinetics of acyclovir (an antiviral agent) following rapid intravenous injection. J Antimicrob Chemother 1981 7 399-404. 

Laskin OL, Clinical pharmacokinetics of acyclovir, Clin. Pharmacokin., 8, 187-201. (1983). 

Weller S, Blum MR, Doucette M, Burnette T, Cederberg DM, Miranda Pd, Smiley ML. Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and... 

S3mtex. A single-dose, pharmacokinetic drug interaction study of oral mycophenolate mofetil and oral acyclovir in normal subjects. Data on file, 1994. 

Chetoni, P. Rossi, S. BurgalassL S. Monti, D. Mariotti, S. Saettone, M.F. Comparison of liposome-encapsulated acyclovir with acyclovir ointment Ocular pharmacokinetics in rabbits. J. Ocul. Pharmacol. Then 2004, 20 (2), 169-177. 

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