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Pharmaceutical Care and Research: 2018; 18(6):434-438
DOI: 10.5428/pcar20180610
Synthesis and in vivo pharmacokinetics study of derivatives of asiatic acid in rats
1. ZHU Bing1(1.Department of Pharmacy,Changhai Hospital,Second Military Medical University,Shanghai 200433,China
2. LI ShanXin1(1.Department of Pharmacy,Changhai Hospital,Second Military Medical University,Shanghai 200433,China )
3. ZHAO NaPing1(1.Department of Pharmacy,Changhai Hospital,Second Military Medical University,Shanghai 200433,China )
4. Mao JunQin2(2.Department of Pharmacy,No.85 Hospital of PLA,Shanghai 200052,China )
5. ZHANG DaZhi3(3.Teaching and Research Section of Organic Chemistry,School of Pharmacy,Second Military Medical University,Shanghai 200433,China )
6. ZHANG Hai4(4.Department of Pharmacy,First Maternity and Infant Hospital Affiliated to Tongji University,Shanghai 201204,China )
7. ZHANG Li1(1.Department of Pharmacy,Changhai Hospital,Second Military Medical University,Shanghai 200433,China chyyy
ABSTRACT  Objective: To design and synthesize the novel derivatives of asiatic acid(AA) and investigate their pharmacokinetic properties of rats in vivo.Methods:Isopropylidene was introduced between C3 and C23,and benzyl was introduced to C28 of AA,then 3,23-O-isopropylidene asiatic acid (A1) and asiatic acid benzyl ester(Z3) were synthesized.The structures of A1 and Z3 were confirmed by 1H-NMR and MS.Twelve rats were randomly divided into two groups: the caudal vein injection group (n=6) and the A1 gavage group (n=6).HPLC-MS method was established to determine the plasma concentration of A1 in rats with Z3 as an internal standard.The plasma concentrations of A1 after caudal vein injection or gavage were determined and pharmacokinetic parameters were calculated.Results:Compared with the pharmacokinetic parameters of AA after gavage,the t1/2 and MRT0-∞ of A1 were significantly prolonged,the cmax and AUC0-∞ of A1 increased by 11.14 fold and 57.51 fold,and the CL of A1 decreased to 6.95%.The absolute bioavailability of A1 was 75.81%,which was 4.67 fold higher than that of AA(16.25%).Conclusion:The pharmacokinetic properties of A1 were significantly superior to those of the derivatives of asiatic acid.For this reason,it was worthy of further research and development.
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ZHU Bing1,LI ShanXin1,ZHAO NaPing1,Mao JunQin2,ZHANG DaZhi3,ZHANG Hai4,ZHANG Li1,. Synthesis and in vivo pharmacokinetics study of derivatives of asiatic acid in rats[J]. Pharmaceutical Care and Research / yao xue fu wu yu yan jiu. 2018; 18(6): 434-438.
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