Itraconazole oral solution and intravenous formulations: a review of pharmacokinetics and pharmacodynamics

Willems, Ludo; Geest, Ronald van der; Beule, K. De

doi:10.1046/j.1365-2710.2001.00338.x

Cited by 194 publications

(128 citation statements)

References 55 publications

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…1,2 Currently, ITZ is also explored as an anticancer agent for patients with metastatic breast cancer and prostate cancer in clinical trials. 3 Oral ITZ formulation has been broadly applied to treat certain…”

Section: Introductionmentioning

confidence: 99%

Development of PLGA-based itraconazole injectable nanospheres for sustained release

Bian¹,

Liang²,

John³

et al. 2013

IJN

View full text Add to dashboard Cite

Purpose Itraconazole (ITZ) is a synthetic triazole antifungal agent, which is widely used for treatment and prevention of fungal infections. The purpose of this study is to develop ITZ-loaded poly(lactic-co-glycolic acid) (PLGA) nanospheres (PLGA-ITZ-NS) as a new sustained-release formulation for intravenous ITZ administration. Materials and methods PLGA-ITZ-NS were prepared by a nanoprecipitation method and optimized by modifying the surfactant poloxamer 188 concentration and PLGA:ITZ ratio. Their physicochemical properties, including size, zeta potential, external morphology and encapsulation efficiency, were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM) and high performance liquid chromatography (HPLC). The effect of the different selected lyoprotectants with various concentrations on NS particles size and surface charge were also assessed. Rapid and sensitive HPLC and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were developed to determine ITZ concentrations in formulation and in rat plasma, respectively. Pharmacokinetics of the optimum PLGA-ITZ-NS formulation was compared with the former commercial Sporanox® injection formulation using rats as the animal model. Noncompartmental pharmacokinetic parameters were obtained by WinNonlin® software. Results Optimal PLGA-ITZ-NS had a mean particle size of about 200 nm with a high homogeneity (polydispersity index ≈0.2), favorable zeta potential (approximately −20 to −30 mV) and encapsulation efficiency (72%). In addition, 2% w/v sucrose was selected as a lyoprotectant for NS freeze-drying. The newly developed LC-MS/MS assay was validated and found to be accurate and precise. The in vivo study showed that the NS formulation has a similar systemic bioavailability to Sporanox® while providing a sustained plasma level (> 100 ng/mL) for up to 24 hours after intravenous administration. Conclusion Our newly developed PLGA-ITZ-NS has shown great sustained release and comparable bioavailability with Sporanox®, therefore having the potential to be an alternative injectable formulation of ITZ.

show abstract

Section: Introductionmentioning

confidence: 99%

Development of PLGA-based itraconazole injectable nanospheres for sustained release

Bian¹,

Liang²,

John³

et al. 2013

IJN

View full text Add to dashboard Cite

show abstract

“…At predetermined time intervals, 0.4 ml of blood was collected from the right femoral artery and centrifuged at 3000 g for 10 min using a centrifuge 5415C (Eppendorf, U.S.A.). 15,35) Blood Sample Analysis Plasma (0.1 ml) was mixed with 0.1 ml of mobile phase solution containing domperidone (100 ng/ml), as an internal standard. Then, 0.01 ml of 1 M NaOH was added and followed by liquid-liquid extraction for 10 min with 1.5 ml of diethyl ether : n-hexane (4 : 1 v/v).…”

Section: )mentioning

confidence: 99%

Enhanced Solubility and Bioavailability of Sibutramine Base by Solid Dispersion System with Aqueous Medium

Jang

Kang

et al. 2010

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Sibutramine [1-(4-chlorophynyl)-N,N-dimethyl-a-(2-methylpropyl)cyclobutane methane amine] is a newer antiobesity drug with a novel mechanism of action.1) It contains a potent inhibitor of the reuptake of noradrenaline (NA), serotonin (5-HT) and may stimulate thermogenesis by its activation of b 3 -adrenoceptors in brown adipose tissue. [2][3][4] In human subjects, sibutramine is rapidly metabolized to an Nmono-desmethyl metabolite (desmethylsibutramine [Metabolite I]) and an N,N-didesmethyl metabolite (didesmethylsibutramine [Metabolite II]). The in vivo effects of sibutramine are predominantly the results of the action of the above 2 metabolites. 4-7)Sibutramine hydrochloride monohydrate is the commercially available formulation of sibutramine with the relatively high solubility of 2.9 mg/ml at pH 5.2 and melting point of 190°C. 4,8) However, sibutramine base with low solubility has not been used in commercial formulation. Various oral formulations of sibutramine such as another salt form such as sibutramine mesylate 9,10) and sibutramine tartrate, 11) solid dispersions with poloxamer [12][13][14] and inclusion complex. 15)One of the well established method for increasing the solubility and bioavailability of poorly water-soluble drugs is solid dispersion.16) Several conventional methods such as melting, solvent evaporation and solvent wetting were reported to prepare solid dispersions. 17,18) However, the solid dispersion prepared by melting method with high temperature might chemically decompose the drugs. 19,20) In the case of solvent evaporation and solvent wetting method, the drug in the solid dispersions changed to amorphous form, resulting that the drug might be unstable. 18) Furthermore, a large amount of hydrophilic carriers against drug in these conventional solid dispersions must be needed to improve the solubility of poorly water-soluble drugs. 21,22) In this study, to improve the bioavailability of poorly water-soluble sibutramine base, various sibutramine baseloaded solid dispersions were prepared with water, hydroxypropylmethyl cellulose (HPMC), poloxamer and citric acid using spray-drying technique. The effect of HPMC, poloxamer and citric acid on the aqueous solubility of sibutramine was then investigated. The physicochemical properties of solid dispersion were investigated using scanning electron microscope (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction. The dissolution and pharmacokinetics in rats of solid dispersion were evaluated compared to the sibutramine hydrochloride monohydrate-loaded commercial product (Reductil ® ). This commercial product is a conventional capsule which contains 100 mg sibutramine hydrochloride monohydrate and is usually taken multiple times a day. Poloxamer has been employed to enhance the solubility and bioavailability of poorly water-soluble drugs. 19,23) HPMC is frequently used in the preparation of conventional pharmaceutical oral dosage form due to its hydrophilic and soft property. 24,25) To develop a novel sibutramine base-...

show abstract

“…macokinetics of ITCZ-OS, and indicated that the interval until the blood level of ITCZ reached a steady state was 14 d. 14) As a rule, we collected blood 14 d or more after the start of oral administration to achieve a trough level. To reduce the patients' physical stress, a portion of blood collected for the purpose of routine clinical examinations was employed as a sample to measure the blood level of ITCZ.…”

Section: Subjectsmentioning

confidence: 99%

Clinical Significance of Measuring the Blood Concentration of Itraconazole Oral Solution in the Field of Hematology

Shimoeda

Nakagawa

Kobayashi

et al. 2010

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Itraconazole (ITCZ), a triazole antifungal agent, is highly fat-soluble. It shows favorable transfer to adipose tissue, but digestive tract absorption is unfavorable.1) In particular, there are marked individual differences in the absorption of capsules. In patients with neutropenia, the absorption rate is reported to be approximately 20%.2,3) To stabilize drug absorption, ITCZ oral solution (ITCZ-OS) containing cyclodextrin as a base was developed. Recently, ITCZ-OS has also been applied in clinical practice in addition to conventional capsules in Japan.Many clinical studies have reported the preventive effects of ITCZ on fungal infection. Some studies indicated that prophylactic therapy with ITCZ-OS significantly decreased the incidence of invasive fungal infection. However, others emphasized that there was no significant decrease. Therefore, the preventive effects of ITCZ-OS remain controversial. [3][4][5][6][7][8][9][10]

show abstract

Itraconazole oral solution and intravenous formulations: a review of pharmacokinetics and pharmacodynamics

Cited by 194 publications

References 55 publications

Development of PLGA-based itraconazole injectable nanospheres for sustained release

Development of PLGA-based itraconazole injectable nanospheres for sustained release

Enhanced Solubility and Bioavailability of Sibutramine Base by Solid Dispersion System with Aqueous Medium

Clinical Significance of Measuring the Blood Concentration of Itraconazole Oral Solution in the Field of Hematology

Contact Info

Product

Resources

About