food effect | Acta Medica Marisiensis

Food-effect study on the pharmacokinetics of indapamide prolonged-release tablets

Maria Codreanu^1,2, Diana Iacob³, Maria Ioana Onofrei^4,5, Ana-Maria Vlase⁶, Dana Maria Muntean¹, Laurian Vlase¹

1. Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Haţieganu”, Cluj-Napoca, Romania
2. Regulatory Affairs Department, Antibiotice SA, Iași, Romania
3. Center for Drug Evaluation, Antibiotice SA, Iași, Romania
4. Clinic of Infectious Diseases, “Sf. Parascheva” Clinical Hospital of Infectious Diseases, Iasi, Romania
5. Department of Infectious Diseases, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
6. Department of Pharmaceutical Botany, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Haţieganu”, Cluj-Napoca, Romania

DOI: 10.2478/amma-2024-0032

Objective: A comparative study was performed to evaluate the food impact on the pharmacokinetics of indapamide 1.5 mg prolonged release tablets (SR).
Methods: The data evaluated were collected from 2 randomized, single dose, 2-way crossover bioequivalence studies with administration of indapamide to healthy Caucasian volunteers under fasting and fed conditions, respectively. Forty-four eligible subjects aged 19–39 years were enrolled in both studies: 22 subjects received indapamide under fasting (study 1) and the other 22 under fed (study 2) conditions. Blood samples were collected following the same schedule before and up to 96.0 hours after drug administration. Blood concentration of indapamide were quantified by a validated LC-MS/MS method. A non-compartmental analysis was used to calculate the pharmacokinetic parameters. Mathematical deconvolution was applied to assess indapamide absorption. Statistical significance for differences in key pharmacokinetic parameters was evaluated using an ANOVA test, with a significance threshold of p < 0.05.
Results: In total, 44 subjects were included in analysis. The outcomes demonstrated that ingestion of food independently reduced the mean of tmax by 4.64 h and increased the value of Cmax by 19.7 ng/mL, while the AUC remained unchanged.
Conclusions: Notably, differences in drug absorption rate obtained after co-administration of indapamide with food had no significant influence in safety and efficacy of the drug.

Effect of Food on the Pharmacokinetics of Gliclazide 60 mg Modified Release Tablet in Healthy Caucasian Volunteers

Diana Pop¹, Ana-Maria Gheldiu¹, Monica Oroian^1,2, Adriana Marcovici², Sandeep Bhardwaj², Arshad Khuroo³, Ravi Kochhar⁴, Laurian Vlase¹

1. Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania
2. Clinical Pharmacology and Pharmacokinetics Department, Terapia S.A-Sun Pharma Company, Cluj-Napoca, Romania
3. Clinical Pharmacology and Pharmacokinetics Department, Gurugram, India
4. R&D Formulation Development, Gurugram, India

DOI: 10.2478/amma-2018-0022

Objective: To evaluate the food effect on glicazide disposition in clinical trials conducted on healthy Caucasian volunteers who were given a new modified release oral formulation of Gliclazide 60 mg developed by Sun Pharmaceutical Industries, India.
Methods: The studies were designed as open-label, randomized, single-dose, crossover studies that consisted of two periods. During each study, venous blood samples were taken before and after drug administration up to 96 hours. Subsequently, individual plasma profiles were determined and non-compartmental method was employed for the assessment of food effect on the pharmacokinetic profile of gliclazide. The statistical significance of differences for the main pharmacokinetic parameters was evaluated by ANOVA test, for p < 0.05 statistical significance was decided. The relative profiles of absorption of gliclazide were obtained by mathematical deconvolution. All calculations were performed by Phoenix WinNonlin®.
Results: High-fat, high-calorie meal decreased gliclazide exposure. The mean maximum plasma concentration decreased with 14%, while the mean total area under the plasma concentration-time profile registered a 17% decrease. The elimination half-lives under fasted and fed conditions were comparable and the time to maximum plasma concentration was shortened under fed condition. Safety evaluation showed that overall gliclazide was well tolerated under both fasted and fed condition.
Conclusions: The statistical analysis revealed the lack of food effect on the new modified release tablets of Gliclazide 60 mg. However, before stating a definite conclusion regarding the food effect on gliclazide pharmacokinetic profile, additional studies on patients with type 2 diabetes mellitus should be conducted.