Pharmacokinetics and plasma protein binding of rutin deca (H-) sulfate sodium

Rutin deca (H-) sulfate sodium (RDS) possesses very good activity as an inhibitor of the complement system of warm-blooded animals and HIV.  An ion-pair coupled with solid-phase extraction technique (IP-SPE) was developed to extract RDS from rat plasma, urine, bile and protein solution samples.  The assay was applied to pharmacokinetics of RDS, including plasma pharmacokinetics, excretion and protein binding studies.  After iv 5, 20 and 100 mg·kg⁻¹ RDS via tail vein in rats, the plasma concentration-time profiles were fitted using 3P97 software.  The average terminal half-life (t_1/2) was 3.432 ± 0.185 2 h.  The relationship of dose and AUC of RDS was linear within the dosage range.  This suggested that the disposition of RDS in rats belong to linear kinetics and the pharmacokinetic parameters of RDS were dose independent.  After iv RDS 20 mg·kg^{−1 in rats, the biliary excretion amount of parent drug amount was only 0.318 1% ± 0.208 7% of given} dosage, and the urinary excretion was 86.0% ± 6.1% in 36 h.  Ultrafiltration techniques were applied to determine the protein binding of RDS in plasma (from SD rat, Beagle dog and human), human serum albumin (HSA) and human α₁-acid glycoprotein (AGP).  The mean protein binding rate in plasma of SD rat, Beagle dog and human plasma of RDS were 80%−90%, in which the range of concentration of RDS was 5 to 100 μg·mL⁻¹.  The protein binding to HSA was 85.7% ± 1.3% and 14.0% ± 3.2% to AGP.