Pharmacokinetics of PFA (trisodium phosphonoformate) after i.v. and p.o. administration to beagle dogs and rabbits.
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.
Ritschel
W A
WA
Grummich
K W
KW
Hussain
S A
SA
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
D000998:Antiviral Agents; D009943:Organophosphorus Compounds; D017245:Foscarnet; D010746:Phosphonoacetic Acid