PREDICTIVE PHARMACOKINETIC MODEL BASED ON THE CORRELATION OF IN VITRO AND IN VIVO SUBLINGUAL ABSORPTION PARAMETERS
Introduction/Abstract
To develop a predictive pharmacokinetic model based on the correlation of in vitro and in vivo sublingual absorption parameters.
Purpose
In vitro permeation studies were performed using model drugs (Caffeine and naproxen) on excised New Zealand white rabbit’s sublingual tissue using modified Franz diffusion cell. The donor and receiver chamber were charged with drug dissolved in McIlvaine buffer pH 6.8 and blank McIlvaine buffer pH 7.4, respectively. Samples were withdrawn at predetermined time intervals and equivalent volume of fresh buffer was replaced. Collected samples were quantified using a validated HPLC method. In vivo studies were conducted in New Zealand white rabbits (n=3). The rabbits were dosed intravenously and sublingually and the blood samples were collected at predetermined intervals of time. Drug was extracted from the plasma using solid phase extraction and analyzed using HPLC equipped with ultraviolet detector. Pharmacokinetic parameters were calculated using WinNonlin (Pharsight®, Mountain View, CA). In vitro and in vivo sublingual absorption parameters such as permeability coefficients and lag time were determined from the plot of cumulative amount permeated vs time and correlated with each other. In vitro permeability coefficient was used to calculate the absorption rate which was employed to generate in vivo plasma concentration-time profile based on intravenous infusion model using Micromath Scientist® software. The fitness of the model was evaluated on the basis of correlation coefficient between calculated and experimental profile.
Method
In vitro and in vivo permeability coefficients were similar for caffeine: (2.10±0.22)×10-5 cm/s and (2.06±0.47)×10-5 cm/s (p>0.05) and naproxen: (1.91±0.44)×10-5 cm/s and (2.34±0.26)×10-5 cm/s (p>0.05), respectively. However, a difference in lag time was observed in two systems viz. in vitro lag time for caffeine and naproxen was 30 and 42 mins while in vivo lag time for both drugs was less than 5 mins. Predicted plasma concentration-time profile using in vitro absorption rate was found to be in good agreement with the experimental profile having a correlation coefficient of 0.99 and 0.97 and coefficient of determination 0.97, 0.88 for naproxen and caffeine, respectively.
Results
Sublingual absorption parameters across in vitro and in vivo system were correlated. In vivo plasma concentration-time profile can be predicted employing in vitro permeability coefficient.
Location
DeRosa University Center, Stockton campus, University of the Pacific
Format
Poster Presentation
PREDICTIVE PHARMACOKINETIC MODEL BASED ON THE CORRELATION OF IN VITRO AND IN VIVO SUBLINGUAL ABSORPTION PARAMETERS
DeRosa University Center, Stockton campus, University of the Pacific
To develop a predictive pharmacokinetic model based on the correlation of in vitro and in vivo sublingual absorption parameters.
