Pharmacokinetic and Metabolic Studies of Retrojusticidin B, a Potential Anti-Viral Lignan, in Rats

Abstract

The pharmacokinetics and metabolism of retrojusticidin B, an anti-HIV reverse transcriptase agent isolated from Phyllanthus myritifolius, were studied in rats. The phase II conjugated metabolites were characterized after solvolysis and enzymatic hydrolysis. The oral bioavailabilities of retrojusticidin B, suspended in Tween 80 and in corn oil, were found to be 22.1 % and 33.1 %, respectively. The elimination half-lives (T_1/2) were 22.9 and 36.2 minutes, respectively. The T_1/2, clearance, and the volume of distribution (Vz) of retrojusticidin B estimated from i. v. measurements were 24.5 min, 2.6 ± 0.4 L/min, and 90.6 ± 6.4 L, respectively. 9,9′-Secoretrojusticidin B was shown to be phase I metabolite.

Abbreviations

AUC:area under the plasma level-time curve

Vz:apparent volume of distribution of the central compartment

Cl:clearance

C_max:maximum peak concentration

T_max:the time to achieve C_max

Key words

Retrojusticidin B - metabolites - pharmacokinetics - bioavailability

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