Pharmacokinetics and tissue distribution of zidovudine in rats following intravenous administration of zidovudine myristate loaded liposomes.
Liposomes accumulating in the reticuloendothelial system (RES) appear to be a promising vehicle to improve the therapeutic index of anti-HIV drugs such as zidovudine (AZT). Since the entrapment efficiency of AZT in liposomes was found to be low and AZT leakage from liposomes is fast, zidovudine myristate (AZT-M) was synthesized as a prodrug, and AZT-M incorporated liposomes in a lyophilized form were prepared with an average diameter of 90 nm and an encapsulation efficiency of 98% after reconstitution. The pharmacokinetic profiles and tissue distribution of AZT after i.v. administration of AZT-M liposomes in rats were investigated, and the results were compared with those after i.v. administration of AZT solution. AZT levels in plasma were significantly higher following application of AZT-M liposomes compared with AZT solution, and AUC0_infinity increased from 5.0 +/- 0.7 micromol x min x ml(-1) to 8.2 +/- 1.7 micromol x min x ml(-1) accordingly. Tissue distribution studies also confirmed higher concentrations of AZT in organs of RES and brain, suggesting that AZT-M liposomes might be promising candidates for therapy of HIV infections.
Jin
S X
SX
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Bi
D Z
DZ
Wang
J
J
Wang
Y Z
YZ
Hu
H G
HG
Deng
Y H
YH
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004187:Disaccharides; D004337:Drug Carriers; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D019814:Myristic Acid / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013055:Spectrophotometry, Infrared; D013535:Suspensions; D014018:Tissue Distribution; D015215:Zidovudine / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D004187:Disaccharides; D004337:Drug Carriers; D008081:Liposomes; D013535:Suspensions; D019814:Myristic Acid; D015215:Zidovudine