Abstract

ASSESSMENT OF FOOD EFFECT ON BIOAVAILABILITY OF DILTIAZEM IN INDIAN POPULATION

Ashvin M. Patel*, Falguni Majmudar, Naveen Sharma and Bhavin N. Patel

ABSTRACT

Objective: Assessment of food effect on bioavailability of diltiazem and it’s pharmacologically active metabolites. Method: Bio-equivalence studies conducted on 24 healthy Indian male subjects in fasting and non-fasting conditions and food effect was assessed. Diltiazem 420mg capsule (TIAZAC capsule of Forest Pharmaceuticals, USA) was administered in fasting and non-fasting conditions. Blood samples were collected serially from time of dosing (0.0hr) to 48.00hr. Solid phase extraction method was used for sample preparation. Validated LC/MS/MS method was used for the quantification. WinNonlin® and SAS® professional softwares used for determination of pharmacokinetic parameters and application of statistics on obtained results. Results: In fasting and non fasting conditions pharmacokinetic parameters for Diltiazem found Cmax 361.449 ng/mL and 350.596 ng/mL, AUCt 7195.74 hr*ng/mL and 4827.51 hr*ng/mL, AUCi 7232.76 hr*ng/mL and 4839.11 hr*ng/mL, Tmax 7.167 hr and 6.000 hr. kel 0.026 hr and 0.031 hr. respectively. For Desacetyl Diltiazem found Cmax 25.181 ng/mL and 24.075 ng/mL, AUCt 684.871 hr*ng/mL and 560.232 hr*ng/mL, AUCi 691.669 hr*ng/mL and 562.694 hr*ng/mL, Tmax 16.583 hr and 11.417 hr. kel 0.020 hr and 0.021 hr. respectively. For N-Desmethyl Diltiazem found Cmax 88.698 ng/mL and 102.631 ng/mL, AUCt 2134.75 hr*ng/mL and 2064.000 hr*ng/mL, AUCi 2153.79 hr*ng/mL and 2077.630 hr*ng/mL, Tmax 8.625 hr and 7.917 hr. kel 0.023 hr and 0.025 hr. respectively. Conclusion:Food significantly affects bioavailability of diltiazem and its active metabolites hence diltiazem should not be administered with food.

Keywords: Diltiazem; food effect; Pharmacokinetics; bioavailability.