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Homsy, Walid; Caillé, Gilles; Souich, Patrick du

doi:10.1023/a:1016217822770

Cited by 20 publications

(1 citation statement)

References 27 publications

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“…Although it is well absorbed across the gastrointestinal tract, it has large inter individual variation and low absolute bioavailability (30% to 40%) due to substantial pre-systemic metabolism. [1][2][3][4] Cytochrome 3A4 (CYP 3A4) and intestinal P-glycoprotein (P-gp) efflux transporter have been proposed as possible candidates for this action. [2][3][4][5]6 The development of novel drug molecule is a time consuming, laborious and expensive process,while the development of new formulations of the existing patented drug molecules opens up vast opportunities for improvement of pharmacotherapeutic characteristics.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Systemic Exposure and Efficacy of Diltiazem from Novel Microemulsion Formulation: Characterization, In vitro Release, In vivo Pharmacokinetic and Efficacy Evaluation

Kamath¹,

Sivakumar²

2017

JYP

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Purpose: Diltiazem, a calcium ion cellular influx inhibitor is known for its limited and variable bioavailability. This study is intended to explore the benefits of microemulsion formulation as oral drug delivery system for immediate release to improve the bioavailability and efficacy of Diltiazem. Methods: Oil in water microemulsion was prepared using the simple water titration method. The optimized formulation was evaluated for physicochemical parameters like viscosity, pH, conductivity and accelerated stability studies. In vitro release, in vivo pharmacokinetics and in vivo efficacy of the optimized diltiazem microemulsion was investigated. Results: The optimized diltiazem microemulsion consisted of 60% water, 5% Almond oil, 35% mixture of surfactant (Tween 80) and cosurfactant (Polyethyne glycol 400) (1:8). The existence of microemulsion region was investigated using pseudoternary phase diagrams. The average particle size by dynamic light scattering technique was found to be 13.8 nm with polydispersity index of 0.474. The optimized microemulsion was found to be thermodynamically stable with in vitro release of 91.82% compared with that of suspension at 55.2%. The peak exposure of diltiazem was 1.23 fold higher and the extent of exposure was found to be 1.24 to 1.29 fold greater for microemulsion compared to the reference tablet formulation when tested in rabbits. The novel formulation was found to have greater efficacy compared to conventional tablet formulation in reducing systolic blood pressure in rats. Conclusion: The diltiazem microemulsion greatly improves the pharmacokinetic parameters and thus improves therapeutic efficacy of diltiazem and could be a potential alternative oral dosage form in therapeutic management of hypertension.

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Section: Introductionmentioning

confidence: 99%

Enhanced Systemic Exposure and Efficacy of Diltiazem from Novel Microemulsion Formulation: Characterization, In vitro Release, In vivo Pharmacokinetic and Efficacy Evaluation

Kamath¹,

Sivakumar²

2017

JYP

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Pharmacokinetic changes of diltiazem and desacetyldiltiazem after oral administration of diltiazem in rabbits with diabetes mellitus induced by alloxan

Choi

Kim

2002

Biopharm & Drug Disp

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Physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics of drugs used to treat hypertension resulting from diabetic complications. Hence, the pharmacokinetics of diltiazem (DTZ) and its metabolite, desacetyldiltiazem (DAD), were investigated after oral administration of DTZ. DTZ, 20 mg/kg, was orally administered to control rabbits and rabbits with fifth day (experiment was performed at fifth day after first and second days intravenous administration of alloxan) and 13th day (experiment was performed at 13th day after first, second, sixth, and 10th days intravenous administration of alloxan) diabetes mellitus induced by alloxan. Impaired kidney and liver functions were observed in both diabetic groups based on plasma chemistry data and/or tissue microscopy. After oral administration of DTZ, the area under the plasma concentration-time curve from time zero to time infinity were 767, 1280 and 1550 ng h/ml for control rabbits and fifth and 13th days diabetes mellitus rabbits, respectively. The values in diabetes mellitus rabbits were significantly different as compared to control rabbits. The terminal half-lives of DTZ were significantly longer in fifth (13.4 h) and 13th (13.0 h) days diabetes mellitus rabbits than that in control rabbits (8.76 h). The renal clearances of DTZ in fifth (0.3161/h/kg) and 13th (0.2641/h/kg) days diabetes mellitus rabbits were significantly slower than that in control rabbits (0.5051/h/kg), and this could be due to impaired kidney function in the diabetes mellitus rabbits. However, other pharmacokinetic parameters of DAD were not significantly different among three groups of rabbits.

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Physiological Modeling of the Small Intestine in Drug Absorption

Pang

Advanced Methods of Pharmacokinetic and Pharmacodynamic Systems Analysis Volume 3

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Abstract: The site of absorption into the intestine modulates the bioavailability of diltiazem and its two active metabolites.

Cited by 20 publications

References 27 publications

Enhanced Systemic Exposure and Efficacy of Diltiazem from Novel Microemulsion Formulation: Characterization, In vitro Release, In vivo Pharmacokinetic and Efficacy Evaluation

Enhanced Systemic Exposure and Efficacy of Diltiazem from Novel Microemulsion Formulation: Characterization, In vitro Release, In vivo Pharmacokinetic and Efficacy Evaluation

Pharmacokinetic changes of diltiazem and desacetyldiltiazem after oral administration of diltiazem in rabbits with diabetes mellitus induced by alloxan

Physiological Modeling of the Small Intestine in Drug Absorption

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