World Journal of
Pharmaceutical and Life Sciences

POPULATION PHARMACOKINETICS OF DOXOPHYLLINE IN BRONCHIAL ASTHMA PATIENTS.

Nithya Punniyakotti*, Hari Prasad B, Uma Maheswara Reddy C, Shobha Rani R Hiremath, Surulivel Rajan M, Ashwin Karanam

ABSTRACT

The intention of our research work was to illustrate the population pharmacokinetics of oral doxophylline (DOXO) in bronchial asthma patients using a population pharmacokinetic (POPK) modeling approach. The study also aimed to identify and evaluate the role of covariates affecting inter-individual variability. Blood samples were collected from 109 patients and DOXO concentrations were analyzed from archived serum samples. Population PK modeling was performed using Phoenix NLME 6.2. The model used to describe the DOXO pharmacokinetics is a two-compartment pharmacokinetic model following first-order absorption and elimination. Boot strapping and visual predictive check methods were implied for model evaluation. The estimated value of clearance, CL and CL2 were 2.49 and 5.19 L/h with an inter-individual variability (IIV) of 1.3 and 4.8% respectively. The estimated value of volume of distribution, V and V2 were found to be 5.6 and 30.2 L with an inter-individual variability of 11.6 and 11% respectively. The absorption rate constant was calculated as 1.59/h with an inter-individual variability of 8.5%. The gender (ISM), smoking habit and co-morbid diabetes were identified as significant covariates affecting the clearance of DOXO. -2Log-likelihood profiling method indicated that the kinetic parameters could be estimated with good precision. Boot strap and visual predictive check model qualification methods proved that the developed model sufficiently described the data observed. This is the first ever population pharmacokinetic study of DOXO in Indian patients. A population pharmacokinetic model from the observed data was developed for doxophylline successfully.

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