Inhaled Loxapine: A New Treatment for Agitation in Schizophrenia or Bipolar Disorder.

Inhaled loxapine: a new treatment for agitation in schizophrenia or bipolar disorder.

Drugs Today (Barc). 2013 Mar; 49(3): 195-201
Owen RT

The treatment of acute agitation in psychiatric patients has traditionally involved the use of oral or intramuscular benzodiazepines, antipsychotics or their combination. However, oral medication may have too slow an onset and while the intramuscular route is faster, it carries an increased risk of adverse events and needle-stick injury. A new delivery modality has been devised using an inhalation-activated, thermally generated drug aerosol which can produce peak plasma concentrations in a few minutes. Using this delivery method, loxapine was assessed for its antiagitation effects in schizophrenia and bipolar I disorder patients. It produced a rapid calming effect without undue sedation. It was generally well tolerated, with dysgeusia being the most common adverse event. HubMed – drug


Florbetapir F 18 for brain imaging of ?-amyloid plaques.

Drugs Today (Barc). 2013 Mar; 49(3): 181-93
Romano M, Buratti E

Recent trends in neurodegeneration research have been aimed at developing new amyloid ligands for the neuroimaging of dementia. Among the positron emission tomography (PET) radiotracers, fluorodeoxyglucose F 18 ((18)F-FDG) is the compound most widely used in the diagnosis of neurodegenerative dementias. However, this compound shows a level of specificity and sensitivity for early Alzheimer’s disease detection that is lower than that provided by high-affinity ligands for ?-amyloid (A?). Among the new widely available fluorine 18 ((18)F)-labeled A? ligands, florbetapir F 18 ((18))F-AV-45; Amyvid™) showed clear qualitative and quantitative correlations between in vivo PET imaging and postmortem histopathologic analysis of A?. Florbetapir F 18 stands out for its high A? affinity and its pharmacokinetic properties that allow 10-minute PET scan imaging within 90 minutes after administration (dose = 370 MBq). Importantly, no safety concerns for florbetapir F 18 were found in preclinical studies. In 2012, the U.S. Food and Drug Administration (FDA) approved Amyvid as a radiotracer helpful for excluding the presence of A? in the brain. It was then approved earlier this year by the European Medicines Agency (EMA). HubMed – drug


Using milk fat to reduce the irritation and bitter taste of ibuprofen.

Chemosens Percept. 2012 Dec 1; 5(3-4): 231-236
Bennett SM, Zhou L, Hayes JE

Bitterness and irritation elicited by pharmaceutically active molecules remain problematic for pediatric medications, fortified foods and dietary supplements. Few effective methods exist for reducing these unpalatable sensations, negatively impacting medication compliance and intake of beneficial phytonutrients. A physicochemical approach to masking these sensations may be the most successful approach for generalizability to a wide range of structurally and functionally unique compounds. Here, solutions of the non-steroidal anti- inflammatory drug, ibuprofen, were prepared in milk products with varying fat content. Our hypothesis, based on other reports of similar phenomena, was that increasing the fat content would cause ibuprofen to selectively partition into the fat phase, thereby reducing interaction with sensory receptors and decreasing adversive sensations. Quantification of the aqueous concentration of ibuprofen was performed using an isocratic HPLC method coupled with an external standard curve. Sensory testing showed a modest but significant decrease (~20%) in irritation ratings between the skim milk (0% fat) and the half-and-half (11% fat) samples, indicating that increased fat may contribute to a reduced sensory response. Bitterness was not reduced, remaining constant over all fat levels. The HPLC results indicate a constant amount of ibuprofen remained in the aqueous phase regardless of fat level, so a simple partitioning hypothesis cannot explain the reduced irritancy ratings. Association of ionized ibuprofen with continuous phase solutes such as unabsorbed protein should be explored in future work. HubMed – drug


Transporting antitumor drug tamoxifen and its metabolites, 4-hydroxytamoxifen and endoxifen by chitosan nanoparticles.

PLoS One. 2013; 8(3): e60250
Agudelo D, Sanyakamdhorn S, Nafisi S, Tajmir-Riahi HA

Synthetic and natural polymers are often used as drug delivery systems in vitro and in vivo. Biodegradable chitosan of different sizes were used to encapsulate antitumor drug tamoxifen (Tam) and its metabolites 4-hydroxytamoxifen (4-Hydroxytam) and endoxifen (Endox). The interactions of tamoxifen and its metabolites with chitosan 15, 100 and 200 KD were investigated in aqueous solution, using FTIR, fluorescence spectroscopic methods and molecular modeling. The structural analysis showed that tamoxifen and its metabolites bind chitosan via both hydrophilic and hydrophobic contacts with overall binding constants of K tam-ch-15 ?=?8.7 (±0.5)×10(3) M(-1), K tam-ch-100 ?=?5.9 (±0.4)×10(5) M(-1), K tam-ch-200 ?=?2.4 (±0.4)×10(5) M(-1) and K hydroxytam-ch-15 ?=?2.6(±0.3)×10(4) M(-1), K hydroxytam – ch-100 ?=?5.2 (±0.7)×10(6) M(-1) and K hydroxytam-ch-200 ?=?5.1 (±0.5)×10(5) M(-1), K endox-ch-15 ?=?4.1 (±0.4)×10(3) M(-1), K endox-ch-100 ?=?1.2 (±0.3)×10(6) M(-1) and K endox-ch-200 ?=?4.7 (±0.5)×10(5) M(-1) with the number of drug molecules bound per chitosan (n) 2.8 to 0.5. The order of binding is ch-100>200>15 KD with stronger complexes formed with 4-hydroxytamoxifen than tamoxifen and endoxifen. The molecular modeling showed the participation of polymer charged NH2 residues with drug OH and NH2 groups in the drug-polymer adducts. The free binding energies of -3.46 kcal/mol for tamoxifen, -3.54 kcal/mol for 4-hydroxytamoxifen and -3.47 kcal/mol for endoxifen were estimated for these drug-polymer complexes. The results show chitosan 100 KD is stronger carrier for drug delivery than chitosan-15 and chitosan-200 KD. HubMed – drug