Plasma pharmacokinetic profile and efficacy of meloxicam administered subcutaneously and intramuscularly to sheep

The main purpose of development pharmaceutical dosage form is to find out the in vivo and in vitro behavior of dosage form. This challenge is overcome by implementation of in-vivo and in-vitro correlation. Application of this technique is economical and time saving in dosage form development. It shortens the period of development dosage form as well as improves product quality. IVIVC reduce the experimental study on human because IVIVC involves the in vivo relevant media utilization in vitro specifications. The key goal of IVIVC is to serve as alternate for in vivo bioavailability studies and serve as justification for bio waivers. IVIVC follows the specifications and relevant quality control parameters that lead to improvement in pharmaceutical dosage form development in short period of time. Recently in-vivo in-vitro correlation (IVIVC) has found application to predict the pharmacokinetic behaviour of pharmaceutical preparations. It has emerged as a reliable tool to find the mode of absorption of several dosage forms. It is used to correlate the in-vitro dissolution with in vivo pharmacokinetic profile. IVIVC made use to predict the bioavailability of the drug of particular dosage form. IVIVC is satisfactory for the therapeutic release profile specifications of the formulation. IVIVC model has capability to predict plasma drug concentration from in vitro dissolution media.

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S.C. injection of recombinant human parathyroid hormone rhPTH(1--84) in thigh provides a more prolonged pharmacokinetic profile and a greater calcemic response when compared with injection in abdomen

Bone Abstracts ◽

10.1530/boneabs.3.pp73 ◽

2014 ◽

Author(s):

John Fox ◽

Roger Garceau ◽

Hjalmar Lagast

Keyword(s):

Parathyroid Hormone ◽

Pharmacokinetic Profile ◽

Human Parathyroid Hormone

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Improved Pharmacokinetic Profile and Anti-Inflammatory Property of a Novel Curcumin Derivative, A50

Letters in Drug Design & Discovery ◽

10.2174/1570180811310060010 ◽

2013 ◽

Vol 10 (6) ◽

pp. 535-542

Author(s):

Xiangjian Chen ◽

Luqing Ren ◽

Xiuhua Zhang ◽

Lu Guo ◽

Jianmin Zhou ◽

...

Keyword(s):

Pharmacokinetic Profile ◽

Anti Inflammatory ◽

Curcumin Derivative

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Hybrids of Coumarin Derivatives as Potent and Multifunctional Bioactive Agents: A Review

Medicinal Chemistry ◽

10.2174/1573406415666190416121448 ◽

2020 ◽

Vol 16 (3) ◽

pp. 272-306

Author(s):

Ioannis Fotopoulos ◽

Dimitra Hadjipavlou-Litina

Keyword(s):

Pharmacological Activity ◽

Biological Activities ◽

Structural Characteristics ◽

Pharmacokinetic Profile ◽

Biologically Active ◽

Hybridization Technique ◽

Coumarin Derivatives ◽

Hybrid Molecules ◽

Pharmacokinetic Properties ◽

Bioactive Agents

Background: Coumarins exhibit a plethora of biological activities, e.g. antiinflammatory and anti-tumor. Molecular hybridization technique has been implemented in the design of novel coumarin hybrids with several bioactive groups in order to obtain molecules with better pharmacological activity and improved pharmacokinetic profile. Objective: Therefore, we tried to gather as many as possible biologically active coumarin hybrids referred in the literature till now, to delineate the structural characteristics in relation to the activities and to have a survey that might help the medicinal chemists to design new coumarin hybrids with drug-likeness and varied bioactivities. Results: The biological activities of the hybrids in most of the cases were found to be different from the biological activities presented by the parent coumarins. The results showed that the hybrid molecules are more potent compared to the standard drugs used in the evaluation experiments. Conclusion: Conjugation of coumarin with varied pharmacophore groups/druglike molecules responsible for different biological activities led to many novel hybrid molecules, with a multitarget behavior and improved pharmacokinetic properties.

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Design, Synthesis, and Pharmacokinetic Evaluation of O-Carbamoyl Tizoxanide Prodrugs

Medicinal Chemistry ◽

10.2174/1573406416666201120102905 ◽

2020 ◽

Vol 16 ◽

Author(s):

Xi He ◽

Wenjun Hu ◽

Fanhua Meng ◽

Xingzhou Li

Keyword(s):

Plasma Concentration ◽

Broad Spectrum ◽

Plasma Concentrations ◽

Antiviral Drug ◽

Systemic Exposure ◽

Pharmacokinetic Profile ◽

Hydroxyl Group ◽

First Pass

Background: The broad-spectrum antiparasitic drug nitazoxanide (N) has been repositioned as a broad-spectrum antiviral drug. Nitazoxanide’s in vivo antiviral activities are mainly attributed to its metabolitetizoxanide, the deacetylation product of nitazoxanide. In reference to the pharmacokinetic profile of nitazoxanide, we proposed the hypotheses that the low plasma concentrations and the low system exposure of tizoxanide after dosing with nitazoxanide result from significant first pass effects in the liver. It was thought that this may be due to the unstable acyloxy bond of nitazoxanide. Objective: Tizoxanide prodrugs, with the more stable formamyl substituent attached to the hydroxyl group rather than the acetyl group of nitazoxanide, were designed with the thought that they might be more stable in plasma. It was anticipated that these prodrugs might be less affected by the first pass effect, which would improve plasma concentrations and system exposure of tizoxanide. Method: These O-carbamoyl tizoxanide prodrugs were synthesized and evaluated in a mouse model for pharmacokinetic (PK) properties and in an in vitro model for plasma stabilities. Results: The results indicated that the plasma concentration and the systemic exposure of tizoxanide (T) after oral administration of O-carbamoyl tizoxanide prodrugs were much greater than that produced by equimolar dosage of nitazoxanide. It was also found that the plasma concentration and the systemic exposure of tizoxanide glucuronide (TG) were much lower than that produced by nitazoxanide. Conclusion: Further analysis showed that the suitable plasma stability of O-carbamoyl tizoxanide prodrugs is the key factor in maximizing the plasma concentration and the systemic exposure of the active ingredient tizoxanide.

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A Comparative Pharmacokinetic Profile of Trahydropalmatine After Oral Administration of its Monomer, Rhizoma Corydalis Alkaloid Extracts and Tong-Bi-Si-Wei-Fang to Rats

Current Pharmaceutical Analysis ◽

10.2174/1573412914666180314122512 ◽

2019 ◽

Vol 15 (4) ◽

pp. 338-345

Author(s):

Lijun Ni ◽

Lu Ding ◽

Liguo Zhang ◽

Shaorong Luan

Keyword(s):

Oral Administration ◽

Panax Notoginseng ◽

Pharmacokinetic Profile ◽

Apparent Volume ◽

Bone Diseases ◽

Glycyrrhiza Uralensis ◽

Pharmacokinetic Property ◽

Time Curve ◽

Concentration Time

Background: Tong-Bi-Si-Wei-Fang (TBSWF) is a candidate formula of Traditional Chinese Medicine (TCM) for treating rheumatoid bone diseases, which is composed of rhizoma corydalis alkaloids, saponins of glycyrrhiza uralensis and panax notoginseng, flavonoids of rhizoma drynariae and glycyrrhiza uralensis. </P><P> Objective: Trahydropalmatine (THP), the main active ingredient of rhizoma corydalis alkaloids, was selected to study in vivo pharmacokinetics and druggability of TBSWF. Methods: The plasma concentration-time (C-T) profiles of THP and the pharmacokinetic property parameters after oral administration of THP monomer, extract of corydalis alkaloids (ECA) and TBSWF to rats, respectively were compared by a fully-validated HPLC method. Results: Compared to the THP monomer, the THP in TBSWF is absorbed faster, resides in the plasma longer and has a similar apparent volume of distribution Vz/F (10~20 L/kg). Compared to THP monomer and THP in TBSWF, the area under the concentration-time curve AUC 0-t of THP in ECA decreases two-third; Vz/F of THP in ECA (85.02 L/kg) is significantly higher than that of THP in TBSWF(p <0.05). Unlike THP monomer and THP in ECA, double peaks are observed in the C-T profile of THP after oral administration of TBSWF. THP in TBSWF exhibits slow release to a certain degree. Conclusion: The interactions among the ingredients of TBSWF promote the adsorption and prolong the residence time of THP in vivo, and provide an explanation for the advantages of TBSWF from the point of pharmacokinetics.

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Amorphous Ropinirole-Loaded Mucoadhesive Buccal Film: A Potential Patient-Friendly Tool to Improve Drug Pharmacokinetic Profile and Effectiveness

Journal of Personalized Medicine ◽

10.3390/jpm10040242 ◽

2020 ◽

Vol 10 (4) ◽

pp. 242

Author(s):

Giulia Di Prima ◽

Giuseppina Campisi ◽

Viviana De Caro

Keyword(s):

Buccal Mucosa ◽

Therapeutic Strategy ◽

Therapeutic Response ◽

Ex Vivo ◽

Hepatic Metabolism ◽

Pharmacokinetic Profile ◽

Promising Candidate ◽

Steady State Condition ◽

Drug Pharmacokinetic ◽

Drug Flux

Nowadays the therapeutic strategies to manage Parkinson’s Disease are merely symptomatic and consist of administering L-DOPA and/or dopamine receptor agonists. Among these, Ropinirole (ROP) is a widely orally-administered molecule, although it is extensively susceptible to hepatic metabolism. Since literature reports the buccal mucosa as a potentially useful route to ROP administration, the development of novel, effective, and comfortable oromucosal formulations should prove desirable in order to both enhance the therapeutic efficacy of the drug and allow a personalized therapeutic strategy able to meet the patient’s needs. The results of the proposed ROP film as a new dosage form show that it is flexible; uniform; and characterized by suitable surface pH; good mucoadhesiveness; low swelling degree; and fast, complete drug release. Moreover, after ex vivo evaluation on a film having an area of 0.282 cm2 and dose of 2.29 mg, the results of drug flux through the buccal mucosa are closely comparable to the amount of ROP that reaches the bloodstream at the steady-state condition after ROP-PR 4 mg oral administration, calculated according to the literature (0.237 mg/cm2·h−1 vs. 0.243 mg/h, respectively). Moreover, drug flux and ROP dose could be accurately modulated time-by-time depending on the patient’s need, by varying the administered disk area. In addition, the proposed ROP film displays no lag time, producing an immediate drug input in the bloodstream, which could result in a prompt therapeutic response. These findings make ROP film a potentially comfortable and patient-friendly formulation, and a promising candidate for further clinical trials.

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Simultaneous Visualization of 161Tb- and 177Lu-Labeled Somatostatin Analogues Using Dual-Isotope SPECT Imaging

Pharmaceutics ◽

10.3390/pharmaceutics13040536 ◽

2021 ◽

Vol 13 (4) ◽

pp. 536

Author(s):

Francesca Borgna ◽

Patrick Barritt ◽

Pascal V. Grundler ◽

Zeynep Talip ◽

Susan Cohrs ◽

...

Keyword(s):

Pharmacokinetic Profile ◽

Somatostatin Analogues ◽

Distribution Coefficients ◽

Spect Imaging ◽

Cell Uptake ◽

Organ Distribution ◽

Dual Isotope ◽

Biodistribution Studies ◽

Simultaneous Visualization

The decay of terbium-161 results in the emission of β¯-particles as well as conversion and Auger electrons, which makes terbium-161 interesting for therapeutic purposes. The aim of this study was to use dual-isotope SPECT imaging in order to demonstrate visually that terbium-161 and lutetium-177 are interchangeable without compromising the pharmacokinetic profile of the radiopharmaceutical. The 161Tb- and 177Lu-labeled somatostatin (SST) analogues DOTATOC (agonist) and DOTA-LM3 (antagonist) were tested in vitro to demonstrate equal properties regarding distribution coefficients and cell uptake into SST receptor-positive AR42J tumor cells. The radiopeptides were further investigated in AR42J tumor-bearing nude mice using the method of dual-isotope (terbium-161/lutetium-177) SPECT/CT imaging to enable the visualization of their distribution profiles in the same animal. Equal pharmacokinetic profiles were demonstrated for either of the two peptides, irrespective of whether it was labeled with terbium-161 or lutetium-177. Moreover, the visualization of the sub-organ distribution confirmed similar behavior of 161Tb- and 177Lu-labeled SST analogues. The data were verified in quantitative biodistribution studies using either type of peptide labeled with terbium-161 or lutetium-177. While the radionuclide did not have an impact on the organ distribution, this study confirmed previous data of a considerably higher tumor uptake of radiolabeled DOTA-LM3 as compared to the radiolabeled DOTATOC.

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