5′-aminocarbonyl phosphonates as new zidovudine depot forms: Antiviral properties, intracellular transformations, and pharmacokinetic parameters

Drug Metabolism and Disposition

Volumn 37, Issue 3, 2009, Pages 494-501

  Khandazhinskaya, Anastasia L ^a   Yanvarev, Dmitry V ^a   Jasko, Maxim V ^a   Shipitsin, Alexander V ^a   Khalizev, Vsevolod A ^a   Shram, Stanislav I ^c   Skoblov, Yuriy S ^b   Shirokova, Elena A ^a   Kukhanova, Marina K ^a  

^a ENGELHARDT INSTITUTE OF MOLECULAR BIOLOGY   (Russian Federation)

^b SHEMYAKIN OVCHINNIKOV INSTITUTE OF BIOORGANIC CHEMISTRY   (Russian Federation)

^c INSTITUTE OF MOLECULAR GENETICS   (Russian Federation)

Author keywords

[No Author keywords available]

Indexed keywords

NIKAVIR; UNCLASSIFIED DRUG; ZIDOVUDINE 5' AMINOCARBONYLPHOSPHONATE; ZIDOVUDINE 5' PHOSPHATE; ZIDOVUDINE DERIVATIVE; ZIDOVUDINE H PHOSPHONATE; RNA DIRECTED DNA POLYMERASE INHIBITOR; ZIDOVUDINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CELL STRAIN HL 60; CONTROLLED DRUG RELEASE; CONTROLLED STUDY; DOG; DOSE TIME EFFECT RELATION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG FORMULARY; DRUG HALF LIFE; DRUG STABILITY; DRUG UPTAKE; FEMALE; HUMAN; HUMAN CELL; LD 50; MALE; MAXIMUM PLASMA CONCENTRATION; MEAN RESIDENCE TIME; MOUSE; NONHUMAN; PRIORITY JOURNAL; RABBIT; TIME TO MAXIMUM PLASMA CONCENTRATION; ANIMAL; BIOAVAILABILITY; BIOTRANSFORMATION; CELL LINE; DELAYED RELEASE FORMULATION; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY;

ANIMALIA; CANIS FAMILIARIS; HUMAN IMMUNODEFICIENCY VIRUS 1; ORYCTOLAGUS CUNICULUS;

ANIMALS; BIOLOGICAL AVAILABILITY; BIOTRANSFORMATION; CELL LINE; DELAYED-ACTION PREPARATIONS; DOGS; FEMALE; MAGNETIC RESONANCE SPECTROSCOPY; MALE; RABBITS; REVERSE TRANSCRIPTASE INHIBITORS; ZIDOVUDINE;

EID: 61449222979     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.108.022269     Document Type: Article

References (16)

1. Beaumont K, Webster R, Gardner I, and Dack K (2003) Design of ester prodrugs to enhance oral absorption of poorly permeable compounds: challenges to the discovery scientist. Curr Drug Metab 4:461-485.
2. Calogeropoulou T, Detsi A, Lekkas E, and Koufaki M (2003) Strategies in the design of prodrugs of anti-HIV agents. Curr Top Med Chem 3:1467-1495.
3. Cato A 3rd, Qian J, Hsu A, Levy B, Leonard J, and Granneman R (1998) Multidose pharmacokinetics of ritonavir and zidovudine in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 42:1788-1793.
4. De Clercq E and Field HJ (2006) Antiviral prodrugs - the development of successful prodrug strategies for antiviral chemotherapy. Br J Pharmacol 147:1l-11.
5. Ias'ko MV, Shipitsin AV, Khandzhinskaia A, Shirokova EA, Sol'ev PN, Pliasunova OA, and Pokrovskiǐ AG (2006) New derivatives of alkyl- and aminocarbonylphosphonic acids containing 3′-azido-3′-deoxythymidine. Bioorg Khim 32:603-608.
6. Kearney BP, Flaherty JF, and Shah J (2004) Tenofovir disoproxil fumarate: clinical pharmacology and pharmacokinetics. Clin Pharmacokinet 43:595-612.
7. Khabriev RU (2005) Guidelines on Experimental (Preclinical) Studies of Novel Pharmacologically Active Compounds, pp 45-47, Medicine, Moscow, Russia.
8. Kravchenko AV (2004) The use of Nikavir in a cocktail for antiretroviral therapy. Meditsynskaya kafedra (Rus) 2:90-92, 166-172.
9. Kukhanova MK and Shirokova EA (2005) 5′-O-Modified nucleoside analogues as prodrugs of anti-HIV agents, in Frontiers in Nucleic Acids, pp 339-341, IHL Press, Tucker, GA.
10. Kurlyandskii BA (2000) Guidelines on preclinical pharmacokinetic studies of novel pharmacologically active compounds and drugs, Medicine, Moscow, Russia.
11. Lyseng-Williams on KA, Reynolds NA, and Plosker GL (2005) Tenofovir disoproxil fumarate: a review of its use in the management of HIV infection. Drugs 65:413-432.
12. Machada J, Salomon H, Oliveira M, Tsoukas C, Krayevsky AA, and Wainberg MA (1999) Antiviral activity and resistance profile of phosphazid-a novel prodrug of AZT. Nucleosides Nucleotides 18:901-906.
13. Shirokova EA, Jasko MV, Khandazhinskaya AL, Ivanov AV, Yanvarev DV, Skoblov YS, Mitkevich VA, Bocharov EV, Pronyaeva TR, Fedyuk NV, et al. (2004) Uncharged AZT and D4T derivatives of phosphonoformic and phosphonoacetic acids as anti-HIV pronucleosides. J Med Chem 47:3606-3614.
14. Skoblov Y, Karpenko I, Shirokova E, Popov K, Andronova V, Galegov G, and Kukhanova M (2004) Intracellular metabolism and pharmacokinetics of 5′-hydrogenphosphonate of 3′-azido-2′,3′- dideoxythymidine, a prodrug of 3′-azido-2′,3′- dideoxythymidine. Antiviral Res 63:107-113.
15. Stańczak A and Ferra A (2006) Prodrugs and soft drugs. Pharmacol Rep 58:599-613.
16. 3H]AZT as a tool for studying metabolic transformations of the nonradioactive counterpart, an inhibitor of HIV replication. Nucleosides Nucleotides Nucleic Acids 26:897-900.