DETERMINATION OF PHARMACOKINETIC PROFILE OF HIGH ORAL DOSE OF AN INNOVATOR BRAND OF ATORVASTATIN IN HEALTHY PAKISTANI VOLUNTEERS

Abstract

Objective: To observe the pharmacokinetic pattern of an innovator atorvastatin formulation, among Pakistani healthy volunteers.

Study Design: Quasi-experimental design.

Place and Duration of Study: It was conducted at research center of Army Medical College, from Dec 2011 to Aug 2012.

Methodology: Twenty-four healthy male volunteers among Pakistani population participated in present study after approval by ethical committee. Each subject was given single dose of two oral tablet of atorvastatin each containing 40mg of atorvastatin after an overnight fast. Blood samples were collected at different time interval up to 48 hours. Atorvastatin was detected in human plasma using validated methodology involving use of highly sensitive HPLC technique. Acetonitrile and 0.05M sodium phosphate buffer were used for mobile phase and for internal standard progesterone was used. Pharmacokinetic indicators, including Cmax, Tmax, t1/2, AUC(0-t), and AUC(0-infinity), were calculated by using Computer program (APO, MWPHARM, and Ver. 3.60).

Results: Pharmacokinetic parameters of 80 mg of tablet atorvastatin were observed in human plasma after oral administration of single oral dose. Drug was detected in plasma with mean peak concentration Cmax 23.97 μg/l and time to reach peak concentration Tmax 3.29 hours. Elimination half-life and elimination rate constant of atorvastatin was 6.11 ± 2.21 hours and 0.13 ± 0.06 l/hr respectively. Applying trapezoidal rule (t=48), for calculating AUC, it was to be found 175.24 ± 59.28 hr/μg/l for AUC0-48 and was 174.28 ± 60.50 hr/μg/l for AUC0–∞ MRT for atorvastatin was calculated as 8.81 ± 3.20 hours.

Conclusion: Pharmacokinetic profile of branded.........