Studies on acyclovir-dextran conjugate: synthesis and pharmacokinetics.
Acyclovir is an antivirus drug which has a good in vitro activity against hepatitis B virus. But because of the low solubility and low distribution in liver, the clinical application of acyclovir in hepatitis B was limited. To increase the solubility and the distribution in liver, acyclovir-dextran conjugate was synthesized by formation of Schiff's base. The solubility of obtained conjugate was 12 times greater than free acyclovir. Acyclovir will be slowly released from the obtained conjugate in pH 7.4 phosphate buffer solution (PBS) at 37 degrees C with a rate constant of 0.0035 hr(-1). Pharmacokinetic studies of acyclovir and acyclovir-dextran conjugate were conducted in mice by i.v. administration. Acyclovir concentrations in plasma, liver and kidney were determined by HPLC method. Relatively higher distribution of acyclovir in liver was observed when i.v. acyclovir-dextran conjugate as compared with i.v. free acyclovir. The results of pharmacokinetic studies indicated that acyclovir-dextran conjugate will be a good candidate to treat hepatitis B.
Tu
Jiasheng
J
Department of Pharmaceutics, China Pharmaceutical University, Nanjing, PR China. jiashengtu@cpu.edu.cn
Zhong
Sha
S
Li
Pengmei
P
D000212:Acyclovir / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D000277:Adjuvants, Pharmaceutic / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D000818:Animals; D000998:Antiviral Agents / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003911:Dextrans / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004339:Drug Compounding; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D012995:Solubility; D013997:Time Factors
D000277:Adjuvants, Pharmaceutic; D000998:Antiviral Agents; D003911:Dextrans; D000212:Acyclovir