Summary
Valaciclovir and famciclovir, two new prodrugs (for aciclovir and penciclovir, respectively) have similar pharmacokinetics in many regards. Both have good but incomplete bioavailability, with the conversion to the active forms taking place in the liver, but by different cytosolic enzymes. Absorption and conversion are consistent in relevant patient groups, including those with liver disease. The pharmacokinetics of both active molecules are also similar in being mainly renally eliminated, a significant component of which is tubular secretion, and elimination half-lives from plasma of approximately 2.2 to 2.5 hours. Dosage adjustment is required in the presence of renal impairment. No clinically important drug interactions have been identified with either drug. The choice between the two agents is likely to depend on clinical factors such as tolerability, safety, efficacy, compliance and possibly cost, rather than on their pharmacokinetics.
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References
Whitley RJ, Gnann JW. Acyclovir: a decade later. N Engl J Med 1992; 327: 782–8
O’Brien JJ, Campoli-Richards DM. Acyclovir: an updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1989; 37: 233–309
Acyclovir data sheet. ABPI data sheet compendium, 1994. Datapharm Publications Ltd, UK
Lewis LD, Fowle ASE, Bittiner SB, et al. Human gastrointestil absorption of acyclovir from tablet duodenal infusion and sipped solution. Br J Clin Pharmacol 1986; 21: 459–62
deMiranda P, Blum MR. Pharmacokinetics of acyclovir after intravenous and oral administration. J Antimicrob Chemother 1983; 12 Suppl. B: 29–37
Beauchamp LM, Orr GF, deMiranda P, et al. Amino acid ester prodrugs of acyclovir. Antiviral Chem Chemother 1992; 3: 157–64
Weiler S, Blum MR, Doucette M, et al. Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers. Clin Pharmacol Ther 1993; 54: 595–605
Soul-Lawton J, Seaber E, On N, et al. Absolute bioavailability and metabolic disposition of the acyclovir prodrug valaciclovir following oral administration to humans. Antimicrob Agents Chemother. In press
deMiranda P, Burnette TC, Smith C, et al. Mechanisms of the enhanced oral bioavailability of acyclovir with the prodrug valacyclovir HC1 (Valtrex™) [abstract]. Presented at the 34th meeting of the ICAAC, Orlando, USA, 1994
deMiranda P, Good SS, Laskin OL, et al. Disposition of intravenous radioactive acyclovir. Clin Pharmacol Ther 1991; 30: 662–72
Maillot F, Bidault R, Rolan P, et al. Pharmacokinetics of valaciclovir and acyclovir in cirrhotic patients following oral administration of valaciclovir [abstract]. Presented at the 13th Interdisciplinary Meeting on Anti-infectious Chemotherapy, Paris, December, 1993
Burnette TC, deMiranda P. Purification and characterisation of an enzyme from rat liver that hydrolyzes 256U87, the L-valyl ester prodrug of acyclovir (Zovirax) [abstract]. Antiviral Res 1993; 20 Suppl. 1: 115
Rolan PE, Maillot F, On NT, et al. The effects of cimetidine and probenecid on the conversion of a valine ester of acyclovir, 256U, to acyclovir and acyclovir renal clearance in healthy volunteers [abstract]. Br J Clin Pharmacol 1993; 35: 533P
Jacobson MA, Gallant J, Wang LH, et al. Phase I trial of valaciclovir, the L-valyl ester of acyclovir, in patients with advanced human immunodeficiency virus disease. Antimicrob Agents Chemother 1994; 38: 1534–40
Wang LH, Schultz M, Weller S, et al. Pharmacokinetics and safety of valaciclovir, an acyclovir prodrug, in geriatric volunteers with and without concomitant diuretic therapy [abstract]. J Am Geriatr Soc 1993; 41 Suppl. 10: SA23
Laskin OL, deMiranda P, King DH, et al. Effects of probenecid on the pharmacokinetics and elimination of acyclovir in humans. Antimicrob Agent Chemother 1982; 21; 804–7
Earnshaw DL, Bacon TH, Darlison SJ, et al. Mode of action of penciclovir in MRC-5 cells infected with herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus. Antimicrob Agents Chemother 1992; 36: 2747–57
Boyd MR, Boon R, Fowles SE, et al. Some biological properties of BRL 42810, a well absorbed prodrug of the antiherpes agent BRL 39123. Antiviral Res 1988; 9: 146
Pue MA, Benet LZ. Pharmacokinetics of famciclovir in man. Antiviral Chem Chemother 1994; 4 Suppl. 1: 47–55
Filer CW, Allen GD, Brown TA, et al. Metabolic and pharmacokinetic studies following oral administration of 14C-famciclovir to healthy subjects. Xenobiotica 1994; 24: 357–68
Clarke SE, Harrell AW, Chenery RJ. The role of aldehyde oxidase in the biotransformation of famciclovir to penciclovir as determined by a human in vitro system [abstract]. Proceedings of the Fifth European ISSX Meeting; Tours, France. Vol. 6. 1993; 61
Pue MA, Pratt SK, Fairless AJ, et al. Linear pharmacokinetics of penciclovir following administration of single oral doses of famciclovir 125, 250, 500 and 750 mg to healthy volunteers. J Antimicrob Chemother 1994; 33: 119–27
Fowles SE, Pierce DM, Prince WT, et al. Effect of food on the bioavailability and pharmacokinetics of penciclovir, a novel antiherpes agent, following oral administration of the prodrug, famciclovir [abstract]. Br J Clin Pharmacol 1990; 29: 620P–621P
Fowles SE, Fairless AJ, Pierce DM, et al. A further study of the effect of food on the bioavailability and pharmacokinetics of penciclovir after oral administration of famciclovir [abstract]. Br J Clin Pharmacol 1991; 32: 657P
Filer CW, Brown TA, Bygate EA, et al. Metabolic and pharmacokinetic studies of sodium [14C]-penciclovir following intravenous administration to healthy subjects [abstract]. Br J Clin Pharmacol 1994; 37: 491P–492P
Pratt SK, Pue MA, Fairless AJ et al. Lack of effect of gender on the pharmacokinetics of penciclovir following single oral doses of famciclovir [abstract]. Br J Clin Pharmacol 1994; 37: 493
Boike SC, Pue MA, Freed MI, et al. Pharmacokinetics of famciclovir in subjects with varying degrees of renal impairment. Clin Pharm Ther 1994; 55: 418–26
Pue MA, Boike SC, Freed MI, et al. Pharmacokinetics of penciclovir in subjects with hepatic insufficiency following oral famciclovir [abstract]. Br J Clin Pharmacol 1993; 36: 177P
Fairless AJ, Pratt SK, Pue MA, et al. An investigation into the potential interaction between theophylline and oral famciclovir in healthy male volunteers [abstract]. Br J Clin Pharmacol 1992; 34: 171P–172P
Pue MA, Saporito M, Laroche J, et al. An investigation of the potential interaction between digoxin and oral famciclovir in healthy male volunteers [abstract]. Br J Clin Pharmacol 1993; 3: 177P
Pratt SK, Fowles SE, Pierce DM, et al. An investigation of the potential interaction between cimetidine and famciclovir in nonpatient volunteers. Br J Clin Pharmacol 1991; 32: 656P–657P
Fowles SE, Pratt SK, Laroche J, et al. Lack of a pharmacokinetic interacton between oral famciclovir and allopurinol in healthy volunteers. Eur J Clin Pharmacol 1994; 46: 355–9
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Rolan, P. Pharmacokinetics of New Antiherpetic Agents. Clin-Pharmacokinet 29, 333–340 (1995). https://doi.org/10.2165/00003088-199529050-00003
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DOI: https://doi.org/10.2165/00003088-199529050-00003