title: Pharmacokinetics of PFA (trisodium phosphonoformate) after i.v. and p.o. administration to beagle dogs and rabbits.
abstract: The antiviral substance PFA (trisodium phosphonoformate) was administered I.V. and P.O. to six young female Beagle dogs, and to white New Zealand rabbits using a randomized crossover design. The pharmacokinetics of PFA was determined from the I.V. concentration-time data by polyexponential curve fitting and by a compartment model independent analysis. In dogs the I.V. data were best fit to three exponential terms. The terminal half-life ranged from 2.6 to 7.9 hours (mean 4.03 h +/- 2.04 S.D.). The mean volumes of distribution for the central compartment, Vc, at steady state, Vss and during the terminal phase, Vz, were 0.15, 0.65 and 1.32 L/kg, respectively. The two methods for generation of pharmacokinetic parameters resulted in practically identical values. After extravascular administration, the concentration-time data were subjected to compartment model independent analysis. The mean absolute bioavailability was 10% after P.O. administration. In rabbits, 11 out of 12 I.V. data sets were best fit to two exponential terms; one set was best fit to 3 exponential terms. The terminal half-life ranged from 1.47 to 4.15 hours (mean 2.18 h +/- 0.87 S.D.). The mean volumes of distribution for Vc, Vss and Vz were 0.32, 0.45 and 0.96 L/kg, respectively. After P.O. dosing the t 1/2 was about 4.4 h and the apparent volume of distribution about 1.2 L/kg. The mean absolute bioavailability after P.O. administration was 95%. The difference in P.O. bioavailability between dog and rabbit may be due to intragastric pH differences between the two species.
authors.forename: W A
authors.initials: WA
authors.lastname: Ritschel
authors.forename: K W
authors.initials: KW
authors.lastname: Grummich
authors.forename: S A
authors.initials: SA
authors.lastname: Hussain
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000378:metabolism*; D001682:Biological Availability; D004285:Dogs; D005260:Female; D017245:Foscarnet; D007275:Injections, Intravenous; D007700:Kinetics; D008954:Models, Biological; D009943:Organophosphorus Compounds / Q000378:metabolism*; D010746:Phosphonoacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D011817:Rabbits; D013045:Species Specificity
chemical_list: D000998:Antiviral Agents; D009943:Organophosphorus Compounds; D017245:Foscarnet; D010746:Phosphonoacetic Acid