Pharmacological and pharmacokinetic profile of the novel ocular hypotensive prodrug CKLP1 in Dutch-belted pigmented rabbits

Angiotensin-(1-7) is an endogenous peptide of the renin-angiotensin system in humans. It has several properties, which make it of great interest for healthcare, such as in systemic/ pulmonary hypertension treatment, insulin resistance improvement, reduction of visceral obesity and cardiac remodeling and arrhythmias. In this randomized double-blinded controlled phase I study we aimed to determine safety, tolerability, and pharmacokinetic properties of the new drug, angiotensin-(1-7) included in Hydroxypropyl β-cyclodextrin [Ang(1-7)/HPβCD)] in healthy adult volunteers, who were recruited in accordance to inclusion and exclusion criteria. Thirty-two volunteers ( 18-40 years-old ) were admitted to a hospital clinical research ward and remained under observation for two days, during which they received a single oral dose of Ang(1-7)HPβCD (equivalent to 0.35, 1.75 or 7.0 mg of the peptide) or placebo (N=8/ group). Vital signs and side effects were recorded according to the study protocol and blood samples were collected to obtain the pharmacokinetic profile of Ang-(1-7using LC/MS/MS. The oral administration of the novel compound Ang-(1-7)/HPβCD caused a dose-dependent elevation in the Ang-(1-7) plasma levels with a Tmax of 6.5±0.6 hours. The medians of the area under the curve for the placebo, 0.35, 1.75 and 7.0 mg doses were (in pg/mL/24 hours): 837.5±139.8 , 1094.4±224.3, 1415.0±187.7 and 1719.4±304.9, respectively. The Cmax for the 0.35, 1.75 and 7.0 mg doses were 26.1±3.17 pg/mL, 30.7±4.18pg/mL and 44.1±7.42 pg/mL, respectively. We did not find any statistically significant differences among the clinical and laboratorial parameters before and after the study. There were few mild side effects reported in the study, not related to the dose: two volunteers reported headache (one in the placebo group and one in the 0,35mg group) and three had dizziness and sweating in the orthostatic position (one in the 0.35 and two in the 1.75mg group). Our data show that the novel Ang-(1-7)/HPβCD formulation allow the absorption of Ang-(1-7), and is safe and well tolerated. Our results open new perspectives for future clinical trials with Ang-(1-7)/HPβCD for the treatment of arterial hypertension and other conditions.

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Safety, Tolerability, and Pharmacokinetic Profile of the Novel Translocator Protein 18 kDa Antagonist ONO-2952 in Healthy Volunteers

Clinical Therapeutics ◽

10.1016/j.clinthera.2015.07.010 ◽

2015 ◽

Vol 37 (9) ◽

pp. 2071-2084 ◽

Cited By ~ 7

Author(s):

Fumitaka Suto ◽

Andrew T. Wood ◽

Michiyoshi Kobayashi ◽

Junji Komaba ◽

Kevin Duffy ◽

...

Keyword(s):

Healthy Volunteers ◽

Pharmacokinetic Profile ◽

Translocator Protein ◽

The Novel ◽

Translocator Protein 18 Kda

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Management of dermatophytosis with a novel itraconazole formulation: a research survey

International Journal of Research in Dermatology ◽

10.18203/issn.2455-4529.intjresdermatol20205591 ◽

2020 ◽

Vol 7 (1) ◽

pp. 33

Author(s):

Susmit Haldar

Keyword(s):

Antifungal Therapy ◽

Fungal Infections ◽

Real Life ◽

Pharmacokinetic Profile ◽

Antifungal Drug ◽

The Novel ◽

Research Survey ◽

Oral Itraconazole ◽

Orally Active ◽

Global Population

Background: Dermatophytic infections are the most prevalent fungal infections, which affect majority of the global population. Indian climate, especially the hot and humid conditions contribute majorly to dermatophytosis. Itraconazole is an orally active triazole antifungal drug, which has demonstrated a broad spectrum of activity and a favourable pharmacokinetic profile. Itraconazole at an appropriate dosage and duration schedule has been reported to be an effective antifungal drug and has achieved optimal results.Methods: The present survey aimed at evaluating the efficacy of the novel itraconazole formulation,I-Tyza 100 [itraconazole 100 mg (Abbott health care pvt ltd)] with multi-particulate in solid dispersion (MPSD) technology in patients with tinea infections. The data collection was based on the proportion of patients presenting in the clinics for tinea infections, the choice and duration of therapy, real life efficacy of the drug, and for understanding the overall antifungal therapy in dermatomycosis.Results: The responses obtained from 177 doctors were evaluated, and statistical analyses were carried out. The results suggested that clinical presentation of patients with tinea infections per week ranged between 30% and 60%. For the management of tinea infections, oral itraconazole was preferred by maximum doctors, followed by terbinafine, griseofulvin and fluconazole. Also, majority of the doctors (83%) opined that MPSD technology could improve therapeutic efficacy of the novel itraconazole formulation.Conclusions: The survey findings indicated that the novel itraconazole formulation is a preferred oral antifungal therapy for the management of tinea infections.

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Phase 1 trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin lymphoma

Blood ◽

10.1182/blood-2001-12-0295 ◽

2002 ◽

Vol 100 (9) ◽

pp. 3101-3107 ◽

Cited By ~ 88

Author(s):

Peter Borchmann ◽

Roland Schnell ◽

Irene Fuss ◽

Oliver Manzke ◽

Thomas Davis ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Phase 1 ◽

Pharmacokinetic Profile ◽

Maximum Tolerated Dose ◽

The Novel ◽

Elimination Half ◽

Heavily Pretreated ◽

Grade Ii ◽

Toxicity Criteria

Abstract CD30 is an excellent target for immunotherapy of Hodgkin lymphoma (HL) because it is overexpressed on Hodgkin and Reed-Sternberg cells. We developed a novel bispecific molecule (BSM) consisting of F(ab′) fragments derived from the murine anti-CD30 monoclonal antibody (MoAb) Ki-4 and the humanized CD64-specific MoAb H22. In vitro experiments of H22xKi-4 demonstrated specific phagocytosis of HL-derived cell lines. Patients (pts) with refractory CD30+ HL were treated with escalating doses of H22xKi-4 at doses of 1, 2.5, 5, 10, and 20 mg/m2/d, respectively (administered intravenously on days 1, 3, 5, and 7). The main study objectives were to determine the maximum tolerated dose and the dose-limiting toxicities of H22xKi-4, to define its pharmacokinetic profile, and to document clinical response. Ten pts were enrolled and are evaluable for toxicity and response. Side effects were transient and mild with hypotension (4 of 10), tachycardia (6 of 10), fatigue (10 of 10), and fever (2 of 10 grade I, 3 of 10 grade II). Pharmacokinetic (PK) data revealed an elimination half-life of 11.1 hours, resulting in a significant accumulation of H22xKi-4. The BSM was shown to bind to both monocytes and malignant cells. Response to H22xKi-4 included 1 complete remission (CR), 3 partial remissions (PR), and 4 pts with stable disease. The new BSM H22xKi-4 can be given safely to pts with refractory CD30+ HL in doses up to 80 mg/m2 per cycle. Although this dose is not the maximum tolerated dose (MTD) as defined by toxicity criteria, surrogate parameters suggest a biologic effective regimen. H22xKi-4 shows activity in heavily pretreated HL patients warranting further clinical evaluation.

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Preparation and Characterization of Novel Anti-cancer drug (s) loaded Co-crystals

Journal of University of Shanghai for Science and Technology ◽

10.51201/jusst/21/09647 ◽

2021 ◽

Vol 23 (09) ◽

pp. 1006-1019

Author(s):

Manju Kharb ◽

◽

Pawan Jalwal ◽

Shikha Rathi ◽

Suresh Kumar ◽

...

Keyword(s):

Pharmacokinetic Profile ◽

Syringic Acid ◽

Cancer Drug ◽

The Novel ◽

Anticancer Chemotherapy ◽

Anti Cancer ◽

Single Method ◽

Vital Component ◽

Viable Approach

Background: Taxanes constitute an important class of anti-cancer agents, which are widely prescribed for the management of cancers like breast, lung and ovaries. These agents belong to Biopharmaceutical Classification System (BCS) class IV, which are neither soluble in the aqueous systems nor permeable across the biological membranes. Objectve: Due to these concerns only, the oral bioavailabilities of these drugs are too low. Looking into these concerns, it was envisaged to develop co-crystals of docetaxel with syringic acid. Methods: For the preparation of co-crystals no single method is used. The methods range from spray drying, crystallization, ultrasonication and freeze drying to supercritical fluid methodologies. Results: The novel co-crystal not only improved the solubility and dissolution rates of the drug, but also resulted in improved pharmacokinetic profile. Conclusion: The present findings provide an economic and viable approach to improve the solubility and absorption profile of a drug, which is a vital component of the anticancer chemotherapy. Such studies provide a hope for the development of approaches to improve the solubility and permeability of drugs with challenges.

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