ABSTRACT
Pharmacokinetics (PK) is the science of the kinetics of drug absorption, distribution and elimination. Statistical methods are usually used for PK parameter estimation producing nonlinear responses where drug effect mechanism is modeled using compartmental approach. In the present study, PK parameters were estimated with nonlinear fixed effects one compartment open model where drug dose and sampling time are covariates and the plasma drug concentration is dependent variable. The PK parameters namely absorption rate constant (a), elimination rate constant (b) and apparent volume of distribution (V) were estimated using nonlinear least square method for each individual separately and for all individuals collectively with longitudinal or multiple response plasma drug concentration-time data obtained from 24 healthy human volunteers with reference drug product of Atorvastatin. The estimates for combined data were â =0.13±0.13hr-1, =0.49±0.13hr-1, =248±0.05L. All the individuals were again stratified into three categories based on Body Mass Index (BMI) and the PK parameters were estimated for each stratum accordingly (stratum-normal: â=0.12±0.17hr-1, =0.47±0.17hr-1, =250.24±0.07L; stratum-overweight: â =0.15±0.24hr-1, =0.47±0.25hr-1, =267.25±0.09L; stratumunderweight: â =0.13±0.13hr-1, =0.49±0.13hr-1, =245±0.05L).
ABSTRACT
Punica granatum has been used for centuries to confer health benefits in a number of inflammatory diseases. Based on its usage in Ayurvedic and Unani medicine, dietary supplements containing pomegranate extract are becoming popular for the treatment and prevention of arthritis and other inflammatory diseases. Pet-ether, dichloromethane and methanol fractions of flower part were chosen for pharmacological screening and analgesic and anti-inflammatory activities in animal model. The anti-inflammatory activity was assessed using the carrageenan-induced rat paw edema model. The analgesic effect was measured in mice using the acetic acid-induced writhing test. In the acetic acid-induced writhing test in mice, pet-ether, dichloromethane and methanol fractions at 200 mg/kg doses level showed 75.77% (p<0.001), 68.56% (p<0.001), 54.64% (p<0.001) inhibition of writhing, respectively. In rat paw edema model induced by carrageenan, pet-ether, dichloromethane and methanol fractions were found to reduce significantly (p<0.001) the formation of edema at the 100 mg/kg dose level and showed 26.92% (p<0.001), 27.97%(p<0.001), 21.85%(p<0.001) inhibition respectively of edema volume at the end of 4 h. Punica granatum possesses evident analgesic and anti-inflammatory activities. The results signify the traditional uses of Punica granatum for inflammation and pain.