Pharmacokinetic and pharmacodynamic evaluation of nano-fixed dose combination for hypertension
Avaneesh K Pandey1, Nusrat Shafiq1, Ritika K Bhandari1
1Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh.
Objective:
The current study was planned to formulate, characterize and evaluate the pharmacokinetics, and pharmacodynamics of a novel 'NanoFDC' comprising hydrochlorothiazide, candesartan (CNDT) and amlodipine.
Methodology:
The candidate drugs were loaded in poly(DL-lactide-co-glycolide) by emulsion-diffusion-evaporation method. The formulations were evaluated for their size, morphology, drug loading and in-vitro release individually. Repeat dose pharmacokinetic and pharmacodynamic study of the nano-fixed dose combination (FDC) was done in dexamethasone-induced animal model.
Results:
The entrapment efficiencies ranged from 44 ± 2.1, 32.2 ± 4 and 40.5 ± 2.6% for amlodipine, hydrochlorothiazide and CNDT, respectively. The nanoparticles ranged in size from 164 to 215 nm. In-vitro release profile of the nanoformulation showed unto 90% release by day 7 in simulated gastric fluid and simulated intestinal fluid, respectively. In pharmacokinetic analysis a sustained-release for 7 days was observed in nano-FDC group. Once weekly oral dosing of nano-FDC of amlodipine, CNDT and hydrochlorothiazide provided adequate antihypertensive effect which was not statistically different from daily dosing of free drugs in dexamethasone-induced animal model.
Conclusion:
Once weekly oral dosing of nano-FDC of amlodipine, CNDT and hydrochlorothiazide provided adequate antihypertensive effect and was not statistically different from daily dosing of free drugs in dexamethasone-induced animal model. This study provides proof of concept of feasibility of once weekly dosing of a nano-FDC comprising three antihypertensive drugs, which can lead to significant improvement in patient adherence to therapy.
More Related Videos
Related Concept Videos
Measurement of Bioavailability: Pharmacodynamic Methods
Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
Dosage Regimen: Fixed Dose
Fixed-dose regimens can be used for various routes of administration, including intravenous (IV) injections and oral medications. For IV administration, a predetermined amount of the drug is...
Determination of Multiple Dosing Parameters: Loading and Maintenance Doses
Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant
Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...


