Pharmacokinetics of antiviral agents in veterinary medicine

Abstract

The pharmacokinetics and brain distribution of zidovudine (3’-azido-3’-deoxythymidine, AZT) and lamivudine ((-)- 2’, 3’-dideoxy-3’-thiacytidine, 3TC) were investigated in healthy cats.|Plasma concentrations of AZT declined rapidly with a terminal half- life of 1.4 ± 0.19, 1.4 ± 0.16 and 1.6 ± 0.26 hr following IV, IG and PO administration of 25 mg/kg AZT to six cats in a three way cross-over study. The area under the curve (AUC) following IV, IG, and PO administration was 64.7 ± 16.6, 42.5 ± 9.41 and 60.5 ± 17.0 mg´h/L, respectively|In a three way cross-over study, the half- lives of 3TC were 1.9 ± 0.21, 2.6 ± 0.66 and 2.7 ± 1.5 hr following IV, IG and PO administration of 25 mg/kg 3TC to six cats. The corresponding AUC was 130 ± 55.2, 115 ± 97.5 and 106 ± 94.9 mg´hr/L.|Both AZT and 3TC were well-absorbed following IG and PO administration.|To determine the distribution of AZT to cerebrospinal fluid (CSF) and brain, plasma, CSF, and brain samples were obtained from five cats that received a 7.0 mg/kg AZT loading dose, followed by three- hour infusion at 14.5 mg/kg/h. Mean (± STD) plasma, CSF, and brain concentrations of AZT at steady state were 26.3 ± 4.21, 8.27 ± 1.21, 6.37 ± 0.61 mg/L, respectively. In six cats, after 7.0 mg/kg loading dose of 3TC, followed by three-hour infusion at 5.5 mg/kg/hr, 3TC concentrations in plasma and CSF at steady states were 17.09 ± 5.26 and 1.73 ± 0.56 mg/L. No 3TC was detected in cat brain.|Pharmacokinetics of (-)-b-D-2,6-diaminopurine dioxolane (DAPD) and its metabolite, (-)-b-D-dioxolane guanosine (DXG) were estimated following administration of 50 mg/kg DAPD intravenously or orally to four adolescent ducks. Most DAPD concentrations were below the limit of quantitation. The AUC of DXG was 17.08 and 13.86 mg×hr/L following intravenous administration of DAPD and 18.26 and 23.11 mg×hr/L following oral administration. The half- life of DXG was 0.33 and 0.56 hr after intravenous DAPD and 0.85 and 0.86 hr following oral dosing of DAPD.