After oral administration valaciclovir is rapidly absorbed from GIT and as a result of metabolism at the "first passage" through the intestine and / or liver due to enzymatic hydrolysis quickly and almost completely (99%) turns into acyclovir and L-valine.
The pharmacokinetics of valaciclovir and acyclovir after ingestion were studied in 14 studies in healthy adult volunteers (n = 283).
When taking valaciclovir hydrochloride at a dose of 1000 mg, the absolute bioavailability of acyclovir is 54.5 ± 9.1% and is not dependent on food intake. Pharmacokinetic parameters after taking different doses of valacyclovir hydrochloride are not proportional to the dose. So, after a single administration of valaciclovir hydrochloride in doses of 100, 250, 500, 750 and 1000 mg Cmax Acyclovir reaches 0.83; 2.15; 3.28; 4.17 and 5.65 μg / ml, AUC - 2.28; 5.76; 11.59; 14.11 and 19.52 h · μg / ml, respectively. After repeated administration of valaciclovir hydrochloride in doses of 250, 500 and 1000 mg four times a day for 11 days Cmax - 2.11; 3.69 and 4.96 μg / ml and AUC - 5.66; 9.88 and 15.70 h · μg / ml, respectively. Tmax is 1.6-2.1 hours. Plasma concentrations of unchanged valacyclovir are low, Cmax below 0.5 μg / ml for all doses studied, after 3 h valaciclovir is no longer detected in the plasma; binding of valaciclovir to plasma proteins - 13.5-17.9%. Acyclovir biotransformiruetsya under the influence of alcohol and aldehyde dehydrogenase and, to a lesser extent, aldehyde oxidase in inactive metabolites. Metabolism valaciclovir / acyclovir is not associated with cytochrome P450 enzymes.
Half-life valaciclovir - less than 30 minutes, half-life Acyclovir after taking valaciclovir hydrochloride is 2.5-3.3 hours (in healthy volunteers with normal renal function), in elderly patients (65 years-83 years) - 3,3-3,7 hours, increases in patients with terminal stage renal failure. Valaciclovir is excreted in urine (45.6%) and with feces (47.12%) for 96 hours. Renal clearance is about 255 ml / min. Of the total amount of valaciclovir excreted by the kidneys, more than 80-89% is eliminated in the form of acyclovir. Less than 1% of valaciclovir is excreted unchanged. After repeated use of valaciclovir in patients with normal renal function acyclovir Do not cumulate.
Dependence of pharmacokinetics parameters on some factors
Diseases of the liver. In patients with moderate liver disease (cirrhosis,proven by biopsy) or severe (biopsy-proven cirrhosis with / without ascites) degree of severity, but not the degree of conversion of valaciclovir to acyclovir, decreases; half-life Acyclovir does not change.
HIV-infected patients. In 9 patients with HIV (number of CD4 cells <150 cells /mm3) with valacyclovir hydrochloride at a dose of 1000 mg 4 times a day for 30 days, pharmacokinetic parameters of valaciclovir and acyclovir did not differ from those observed in healthy volunteers.
Teratogenicity. Valacyclovir did not have a teratogenic effect in rats and rabbits when administered at doses of 400 mg / kg during organogenesis (with plasma concentrations exceeding those in humans by 10 and 7 times, respectively).
Fertility. Valacyclovir did not cause impairment in fertility in males and female rats given an oral dose of 200 mg / kg /day (in this case, the concentration in the blood exceeded that in humans by 6 times).