Pharmacokinetic Parameters Determined For A Fluoroquinolone In The Eye Of Rabbits And Multiple Dosage Regimens Prediction

Abstract

 

Purpose:

 

Determine pharmacokinetic parameters of the compound in study after a single dose. Use the single dose pharmacokinetic parameters to predict the steady-state of multiple dosage regimens for the determination of an appropriate dosage interval.

 

Methods:

 

There were used 54 male New Zeland white Rabbits with a weight between 2.0 and 3.0 kg, using 9 rabbits per time, the dosage administered was 30 μL of quinolone solution 0.3%, the Rabbits were sacrificed at the corresponding time 15, 30, 60, 90, 120 and 180 minutes, following the extraction of the humor aqueous. The concentration of the quinolone was determined using HPLC coupled to an UV detector. The pharmacokinetics parameters were determined using first order reaction equations and one compartment model. For the multiple dosage prediction was applied the principle of superposition which allows to project the concentration-time curve of a drug after several consecutive doses based on the drug concentration-time curve obtained after a single dose.

 

Results:

 

Pharmacokinetics parameters were obtained: absorption constant k_a=1.70008hr^-1, elimination constant k=0.3078hr^-1, fraction of dose absorbed F=0.002. Using this parameters concentration curves for different dosage intervals were constructed.

 

Conclusions:

 

The MIC₉₀ for most of the quinolones is between 100-2000 ng/mL. An appropriate dosage interval for reaching therapeutic levels is every 4 hours in which the steady-state predicted is between C_min=362 ng/mL and C_max=751 ng/mL, this steady-state was reached after the fourth dosage.  

 

 

Keywords: antibiotics/antifungals/antiparasitics • aqueous • anterior chamber