Effects of fluconazole on the pharmacokinetics and pharmacodynamics of antimony in cutaneous leishmaniasis-infected hamsters

摘要: Abstract Pentavalent antimony (Sb V ) compounds are the drugs of choice for treatment all forms leishmaniasis. For 20 years there has been an interest in antifungal azoles treating leishmaniasis, with variable success. In current study, we examined effects co-administration fluconazole (FLZ) on pharmacokinetics and pharmacodynamics Sb cutaneous leishmaniasis-infected hamsters. Hamsters were divided into four groups. All hamsters injected 0.1mL 1×10 8 promastigotes/mL right foot Day 1. Treatment was started 5 days after infection. The group received 80mg/kg/day Pentostam ® intramuscularly whilst FLZ 20mg/kg/day orally 14 days. combination both at above mentioned doses Animals control no treatment. infected footpads measured Days 1 14. A pharmacokinetic study conducted treatment, representing single- multiple-dose pharmacokinetics, respectively. Blood samples collected different time intervals up to 24h. determined using flameless atomic absorption spectrophotometry. Pharmacokinetic parameters calculated a non-compartmental analysis. single-dose statistically significant difference any when given alone or FLZ. However, increase peak plasma concentration ( C max (three-fold) area under concentration–time curve (AUC) (four-fold) observed co-administered prolongation terminal half-life from 1.63 8.67h P as by footpad sizes. conclusion, did not improve therapeutic effect concomitantly despite blood elimination .