Disease relevance of Cyclic-hpmpc

• CONCLUSIONS: Of the HPMP series, the cyclic analogue of HPMPC (cHPMPC) and HPMPC are the least toxic of the compounds that show potent anti-human cytomegalovirus activity (HCMV) [1].
• Two groups of six patients received a single dose of cyclic HPMPC at 1.5 or 3.0 mg/kg of body weight by each of the oral and intravenous routes in a random order with a 2-week washout period between administrations [2].
• The pharmacokinetics and bioavailability of 1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosi ne (cyclic HPMPC) were examined at four doses in 22 patients with human immunodeficiency virus infection [2].
• CONCLUSIONS: Although cyclic HPMPC is reported to exhibit reduced nephrotoxicity in vivo, it is also less potent than cidofovir against orthopoxvirus infections [3].
• Intraperitoneal doses of 40, 80 and 160 mg/kg cidofovir significantly reduced mortality from vaccinia virus infections, compared to doses of 80 and 160 mg/kg cyclic HPMPC [3].

High impact information on Cyclic-hpmpc

• The oral bioavailabilities of cyclic HPMPC were 1.76% +/- 1.48% and 3.10% +/- 1.16% with the administration of doses of 1.5 and 3.0 mg/kg, respectively (n = 6 per dose) [2].
• The pharmacokinetics of cyclic HPMPC were independent of dose over the dose range of 1.5 to 7.5 mg/kg [2].
• Pharmacokinetics, bioavailability, metabolism, and tissue distribution of cidofovir (HPMPC) and cyclic HPMPC in rats [4].
• To examine possible naturally occurring drug resistance among a large number of variola isolates obtained from different geographical regions and at different times, we examined the sensitivity of 35 different strains of variola as well as other orthopoxviruses to a subset of three of the most active compounds: cidofovir, cHPMPC, and ribavirin [5].
• Antiviral treatment with cyclic HPMPC (cHPMPC) for 7 days significantly reduced mortality (1/20 versus 14/20, P<0.001) and viral replication but did not improve weight gain [6].

Biological context of Cyclic-hpmpc

• Treatment of SV40- and adenovirus-transformed cells with ANPs resulted in the inhibition of cell proliferation as a function of time, similar to that observed with HPV-positive cells, HPMPC and cHPMPC being the most potent antiproliferative agents [7].
• Cidofovir accounted for 2 to 12% of the total plasma AUC for butyl-, cyclohexyl- and phenethyl-salicylyl esters of cyclic HPMPC [8].

Anatomical context of Cyclic-hpmpc

• In efficacy studies in immune compromised guinea pigs challenged with a virulent salivary gland passaged guinea pig CMV, CHPMPC treatment significantly reduced mortality resulting from disseminated virus infection [9].

Associations of Cyclic-hpmpc with other chemical compounds

• Concentrations in kidney at 24 hr after iv administration of 5 mg/kg were approximately 20-fold higher for cidofovir (6.6 micrograms-eq/g) than for cyclic HPMPC, whereas levels of radioactivity in the remaining tissues were similar for both drugs [4].
• Development plans of other agents such as cyclic HPMPC and lobucavir have been put on hold by their respective manufacturers [10].

Analytical, diagnostic and therapeutic context of Cyclic-hpmpc

• The maximum concentrations of cyclic HPMPC in serum were 0.036 +/- 0.021 and 0.082 +/- 0.038 microgram/ml after the oral administration of doses of 1.5 and 3.0 mg/kg, respectively [2].

References