Differential Pharmacokinetics of Digoxin in Elderly Patients

Digoxin remains one of the most commonly prescribed of all cardiac medications. The main indications for digoxin usage include atrial fibrillation and heart failure; both these conditions are more prevalent in older patients. Given the aging population and the increasing incidence of heart failure we would expect prescribing of digoxin to remain as frequent or to even increase in older patients. Older patients are also more likely to develop toxicity and diagnosis of digoxin toxicity can be difficult in this group. Numerous components contribute to the development of toxicity in older patients, ranging from aging-related changes in renal function or body mass to polypharmacy and possible interactions with digoxin. It is therefore important to understand how the pharmacokinetics of digoxin may be altered in the older population. Application of basic pharmacological principles may be helpful in anticipating these problems. This review describes the pharmacokinetics of digoxin, the changes in pharmacokinetics with increasing age and how concomitant disease states or drug interactions may affect the pharmacokinetics of digoxin. Greater knowledge about the causes and prevention of digoxin toxicity should further reduce the morbidity and mortality arising from digoxin toxicity, especially in the elderly population.
For over 200 years debate has raged regarding the use of digitalis glycosides in cardiac disease. At present digoxin is the most commonly prescribed digitalis compound. This review describes the pharmacokinetics of digoxin and in particular how they are altered with increasing age. When considering the elderly population it is important to recognise the heterogeneity of response in this group, therefore there are no rules, with regards to prescribing, that can apply to the entire elderly population.

Differential cross section measurements for elastic scattering of electrons from Ar2+ and Xe2+

A crossed-beams energy-loss spectrometer has been used to investigate angular distributions for electron scattering from Ar2+ and Xe2+ ions, at a collision energy of 16 eV. For Ar2+ the measurements are compared with the predictions of a partial waves calculation based on a semi-empirical potential, where it is shown that the interference term governs the position of the observed minimum in the angular distribution.

Cloning of the (Thr6)-phyllokinin precursor from Phyllomedusa sauvagei skin confirms a non-consensus tyrosine 0-sulfation motif.

Nine bradykinin-related peptides were identified in Phyllomedusa sauvagei skin secretion using QTOF MS/MS fragmentation sequencing. The major peptides were (Thr6)-bradykinin, (Hyp3, Thr6)-bradykinin, (Thr6)-phyllokinin and (Hyp3, Thr6)-phyllokinin. The phyllokinins occurred in both sulfated and non-sulfated forms. All (Thr6)-substituted bradykinins/phyllokinins could be generated from a common precursor by differential post-translational processing and modification. The open-reading frame of the cloned precursor cDNA consisted of 62 amino acid residues with a single bradykinin/phyllokinin coding sequence located at the C-terminus. Structural features included a Glu-Arg processing site at the N-terminus of the bradykinin/phyllokinin domain and the absence of an acidic amino acid residue adjacent to the C-terminal Tyr residue in the phyllokinins. However, the neutral amino acid residue (Ile) at position -1 and the basic amino acid residue (Arg) at position -2 from the Tyr residue, constitute a sulfation motif previously identified only in a protochordean.

The manufacture and characterisation of hot-melt extruded enteric tablets

The aim of this highly novel study was to use hot-melt extrusion technology as an alternative process to enteric coating. In so doing, oral dosage forms displaying enteric properties may be produced in a continuous, rapid process, providing significant advantages over traditional pharmaceutical coating technology. Eudragit (R) L100-55, an enteric polymer, was pre-plasticized with triethyl citrate (TEC) and citric acid and subsequently dry-mixed with 5-aminosalicylic acid, a model active pharmaceutical ingredient (API), and an optional gelling agent (PVP (R) K30 or Carbopol (R) 971P). Powder blends were hot-melt extruded as cylinders, cut into tablets and characterised using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and dissolution testing conducted in both pH 1.2 and pH 6.8 buffers. Increasing the concentration of TEC significantly lowered the glass transition temperature (T,) of Eudragit (R) L100-55 and reduced temperatures necessary for extrusion as well as the die pressure. Moreover, citric acid (17% w/w) was shown to act as a solid-state plasticizer. HME tablets showed excellent gastro-resistance, whereas milled extrudates compressed into tablets released more than 10% w/w of the API in acidic media. Drug release from HME tablets was dependent upon the concentration of TEC, the presence of citric acid, PVP K30, and Carbopol (R) 971P in the matrix, and pH of the dissolution media. The inclusion of an optional gelling agent significantly reduced the erosion of the matrix and drug release rate at pH 6.8; however, the enteric properties of the matrix were lost due to the formation of channels within the tablet. Consequently this work is both timely and highly innovative and identifies for the first time a method of producing an enteric matrix tablet using a continuous hot-melt extrusion process.

Modulated temperature differential scanning calorimetry and its application to freeze-drying

MTDSC is a software modification of the traditional DSC thermal analysis technique that allows more accurate determination of the glass transition as well as measurement of the endothermic relaxation that often accompanies the transition. The glass transition is an essential parameterboth of the original frozen solution and of the end product. Measurement of endothermic relaxation allows the determination of molecularrelaxation times in the freeze-dried product that may be useful in predicting the effect of formulation variables and storage conditions on physical stability.

On solvability of linear differential equations in ${\Bbb R}^{\Bbb N}$

We construct $x^0$ in ${\Bbb R}^{\Bbb N}$ and a row-finite matrix $T=\{T_{i,j}(t)\}_{i,j\in\N}$ of polynomials of one real variable $t$ such that the Cauchy problem $\dot x(t)=T_tx(t)$, $x(0)=x^0$ in the Fr\'echet space $\R^\N$ has no solutions. We also construct a row-finite matrix $A=\{A_{i,j}(t)\}_{i,j\in\N}$ of $C^\infty(\R)$ functions such that the Cauchy problem $\dot x(t)=A_tx(t)$, $x(0)=x^0$ in ${\Bbb R}^{\Bbb N}$ has no solutions for any $x^0\in{\Bbb R}^{\Bbb N}\setminus\{0\}$. We provide some sufficient condition of solvability and of unique solvability for linear ordinary differential equations $\dot x(t)=T_tx(t)$ with matrix elements $T_{i,j}(t)$ analytically dependent on $t$.