Exploring the Relationship of Drug BCS Classification, Food Effect, and Gastric pH-Dependent Drug Interactions

2021 ◽  
Vol 24 (1) ◽  
Author(s):  
Katie Owens ◽  
Sophie Argon ◽  
Jingjing Yu ◽  
Xinning Yang ◽  
Fang Wu ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Food Effect ◽  
Gastric Ph ◽  
Ph Dependent ◽  
Relationship Of ◽  
The Relationship

P0009EVALUATION OF THE POTENTIAL FOR DRUG INTERACTIONS WITH VEVERIMER

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jun Shao ◽  
Dawn Parsell ◽  
Robert Guttendorf ◽  
Yick Sen Wu ◽  
Li Tsao ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Healthy Subjects ◽  
Gastric Ph ◽  
Pharmacokinetic Parameters ◽  
In Vitro Binding ◽  
Vitro Binding ◽  
Direct Binding ◽  
Ph Dependent

Abstract Background and Aims Veverimer is an investigational drug being developed as an orally administered hydrochloric acid binder for the treatment of metabolic acidosis associated with chronic kidney disease (CKD). In clinical studies, treatment with veverimer safely and effectively increased serum bicarbonate and improved objective and subjective measures of physical functioning1-3. Veverimer, a free-amine polymer, is not systemically absorbed; therefore, its potential for drug-drug interactions (DDIs) is limited to those that occur in the gastrointestinal (GI) tract (i.e., direct binding or indirect effects resulting from transient increases in gastric pH). We assessed the potential for DDIs with veverimer both in vitro and in vivo in healthy subjects. Methods In vitro binding to veverimer was evaluated with 16 drugs of varying molecular weight and charge. In a separate study, the effect of veverimer on gastric pH was measured continuously in vivo in healthy subjects using a microelectrode pH probe placed in the gastric compartment. Human DDI studies were conducted with 4 orally administered drugs, including those that demonstrated the most in vitro binding to veverimer and those with pH-dependent solubility (furosemide, aspirin, warfarin, dabigatran). Results Veverimer did not bind to any of the positively charged, neutral or zwitterionic drugs tested in vitro. It bound to 3 small (MW <332 Da), negatively charged drugs (aspirin, ethacrynic acid, furosemide); these interactions were reduced or eliminated in the presence of physiologically relevant concentrations of chloride. Neither furosemide nor aspirin showed clinically meaningful changes in pharmacokinetic parameters when coadministered with veverimer in human DDI studies (Figure 1). Veverimer increased gastric pH by ∼3.0 and 1.5 pH units in fasted and fed subjects, respectively. The increase in gastric pH was short-lived, with a peak within 1 hour after dosing and a return to baseline after ∼1.5 hours and ∼3 hours under fasting and fed conditions, respectively. The effect of veverimer on gastric pH was similar in the presence and absence of omeprazole. No clinically meaningful changes in systemic exposure, as indicated by Cmax and AUC, were observed when 3 drugs with pH-dependent solubility were coadministered with veverimer in human DDI studies (Figure 1). Conclusions In human DDI studies, we observed: a) no effect of veverimer on the bioavailability of drugs with physicochemical characteristics most susceptible to direct binding to the polymer; b) small, short-lived effects of veverimer on gastric pH; and c) no effect of veverimer on the bioavailability of drugs with pH-sensitive solubility. Therefore, it is concluded that there is a negligible risk of veverimer involvement in clinically significant DDIs.

The relationship of the scleractinian corals to the rugose corals

Paleobiology ◽  
1980 ◽  
Vol 6 (02) ◽  
pp. 146-160 ◽  
Author(s):  
William A. Oliver
Keyword(s):  
Critical Points ◽  
Scleractinian Corals ◽  
Convincing Evidence ◽  
Early Triassic ◽  
Rugose Corals ◽  
History Of ◽  
The Subject ◽  
Relationship Of ◽  
The Relationship ◽  
Biologic Factors

The Mesozoic-Cenozoic coral Order Scleractinia has been suggested to have originated or evolved (1) by direct descent from the Paleozoic Order Rugosa or (2) by the development of a skeleton in members of one of the anemone groups that probably have existed throughout Phanerozoic time. In spite of much work on the subject, advocates of the direct descent hypothesis have failed to find convincing evidence of this relationship. Critical points are:(1) Rugosan septal insertion is serial; Scleractinian insertion is cyclic; no intermediate stages have been demonstrated. Apparent intermediates are Scleractinia having bilateral cyclic insertion or teratological Rugosa.(2) There is convincing evidence that the skeletons of many Rugosa were calcitic and none are known to be or to have been aragonitic. In contrast, the skeletons of all living Scleractinia are aragonitic and there is evidence that fossil Scleractinia were aragonitic also. The mineralogic difference is almost certainly due to intrinsic biologic factors.(3) No early Triassic corals of either group are known. This fact is not compelling (by itself) but is important in connection with points 1 and 2, because, given direct descent, both changes took place during this only stage in the history of the two groups in which there are no known corals.

Skeletal elements of crinoid echinoderms: High-resolution structural and microanalytical results

1983 ◽  
Vol 41 ◽  
pp. 194-195
Author(s):  
D. F. Blake ◽  
L. F. Allard ◽  
D. R. Peacor
Keyword(s):  
High Resolution ◽  
Marine Invertebrates ◽  
Sea Urchins ◽  
Structural Features ◽  
Sea Stars ◽  
High Resolution Tem ◽  
Relationship Of ◽  
The Relationship ◽  
Insight Into

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.

Studies on Leukemogenic and Sarcomagenic Viruses

1970 ◽  
Vol 28 ◽  
pp. 156-157
Author(s):  
Leon Dmochowski
Keyword(s):  
Electron Microscopy ◽  
Electron Microscope ◽  
Morphological Properties ◽  
Mode Of Development ◽  
Relationship Of ◽  
The Relationship

Electron microscopy has proved to be an invaluable discipline in studies on the relationship of viruses to the origin of leukemia, sarcoma, and other types of tumors in animals and man. The successful cell-free transmission of leukemia and sarcoma in mice, rats, hamsters, and cats, interpreted as due to a virus or viruses, was proved to be due to a virus on the basis of electron microscope studies. These studies demonstrated that all the types of neoplasia in animals of the species examined are produced by a virus of certain characteristic morphological properties similar, if not identical, in the mode of development in all types of neoplasia in animals, as shown in Fig. 1.

The relationship of IGE receptor topography to signaling activity in RBL-2H3 mast cells

1991 ◽  
Vol 49 ◽  
pp. 236-237
Author(s):  
J.R. Pfeiffer ◽  
J.C. Seagrave ◽  
C. Wofsy ◽  
J.M. Oliver
Keyword(s):  
Mast Cells ◽  
Protein A ◽  
Scattered Electron ◽  
Ige Receptor ◽  
Receptor Complexes ◽  
Ige Binding ◽  
Electron Imaging ◽  
Small Clusters ◽  
Relationship Of ◽  
The Relationship

In RBL-2H3 rat leukemic mast cells, crosslinking IgE-receptor complexes with anti-IgE antibody leads to degranulation. Receptor crosslinking also stimulates the redistribution of receptors on the cell surface, a process that can be observed by labeling the anti-IgE with 15 nm protein A-gold particles as described in Stump et al. (1989), followed by back-scattered electron imaging (BEI) in the scanning electron microscope. We report that anti-IgE binding stimulates the redistribution of IgE-receptor complexes at 37“C from a dispersed topography (singlets and doublets; S/D) to distributions dominated sequentially by short chains, small clusters and large aggregates of crosslinked receptors. These patterns can be observed (Figure 1), quantified (Figure 2) and analyzed statistically. Cells incubated with 1 μg/ml anti-IgE, a concentration that stimulates maximum net secretion, redistribute receptors as far as chains and small clusters during a 15 min incubation period. At 3 and 10 μg/ml anti-IgE, net secretion is reduced and the majority of receptors redistribute rapidly into clusters and large aggregates.

Severe Paradoxical Dysphonia in Two Young Women

1993 ◽  
Vol 2 (3) ◽  
pp. 52-55 ◽  
Author(s):  
Michael Collins ◽  
Robert McDonald ◽  
Robert Stanley ◽  
Timothy Donovan ◽  
C. Frank Bonebrake
Keyword(s):  
Young Women ◽  
Theoretical Basis ◽  
Therapeutic Regimen ◽  
Instrumental Data ◽  
Relationship Of ◽  
The Relationship

This report describes an unusual and persistent dysphonia in two young women who had taken a therapeutic regimen of isotretinoin for intractable acne. We report perceptual and instrumental data for their dysphonia, and pose a theoretical basis for the relationship of dysphonia to this drug. We also provide recommendations for reducing the risk of acquiring a dysphonia during the course of treatment with isotretinoin.

Establishing a Group Educational Session for Hyperacusis Patients

2019 ◽  
Vol 28 (2) ◽  
pp. 245-250
Author(s):  
Ann E. Perreau ◽  
Richard S. Tyler ◽  
Patricia C. Mancini ◽  
Shelley Witt ◽  
Mohamed Salah Elgandy
Keyword(s):  
Therapeutic Process ◽  
Treatment Options ◽  
Clinical Group ◽  
Education Session ◽  
Group Approach ◽  
Treatment Protocols ◽  
Educational Session ◽  
Evidence Based Treatment ◽  
Relationship Of ◽  
The Relationship

Purpose Audiologists should be treating hyperacusis patients. However, it can be difficult to know where to begin because treatment protocols and evidence-based treatment studies are lacking. A good place to start in any tinnitus and hyperacusis clinic is to incorporate a group educational session. Method Here, we outline our approach to establishing a hyperacusis group educational session that includes specific aspects of getting to know each patient to best meet their needs, understanding the problems associated with hyperacusis, explaining the auditory system and the relationship of hyperacusis to hearing loss and tinnitus, describing the influence of hyperacusis on daily life, and introducing treatment options. Subjective responses from 11 adults with hyperacusis, who participated in a recent clinical group education session, were discussed to illustrate examples from actual patients. Conclusions Due to the devastating nature of hyperacusis, patients need to be reassured that they are not alone and that they can rely on audiologists to provide support and guidance. A group approach can facilitate the therapeutic process by connecting patients with others who are also affected by hyperacusis, and by educating patients and significant others on hyperacusis and its treatment options. Supplemental Material https://doi.org/10.23641/asha.8121197

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