Pharmacokinetics and tissue distribution of long circulating liposomal formulation of 2′,3′-dideoxyinosine

• Published in: International journal of pharmaceutics 1997-06, Vol.152 (1), p.89-97
• Main Authors: Dipali, Satish R., Lin, Yuh-Jing, Ravis, William R., Betageri, Guru V.
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Dideoxyinosine; General pharmacology; Liposome; Long circulating; Medical sciences; Multilamellar; Pharmaceutical technology. Pharmaceutical industry; Pharmacokinetics; Pharmacology. Drug treatments; Unilamellar
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(97)00070-7

The pharmacokinetic profiles and tissue distribution, after single bolus intravenous doses of 2′,3′-dideoxyinosine (ddI) as a solution, a conventional liposomal formulation (without polyethylene glycol) of ddI and a long circulating liposomal formulation of ddI, were determined using rat as the animal model. Total ddI concentrations displayed multicompartment features following the conventional liposome preparation and appeared one compartment after the long circulating formulation. The ddI levels after the non liposomal preparation followed a one compartment model. The conventional liposomes showed a much greater volume of distribution compared to the long circulating liposomes and subsequently a longer t 1/2. Due to the size of the conventional liposomes, these could not penetrate the fenestrated capillaries of the liver and thus had a lower accumulation in this tissue. Opsonization of these liposomes probably led to higher accumulation of the encapsulated ddI in the spleen, compared to when ddI was administered in a non liposomal form. The long circulating liposomes, on the other hand, provided a barrier to opsonin action and consequently had reduced accumulation in these tissues. The ddI levels in the pancreas were very low compared to the serum concentration after administration of the long circulating liposomes suggesting possible reduction of pancreatitis, an adverse effect of ddI.