Tolerability and efficacy of colestipol hydrochloride for accelerated elimination of teriflunomide.

BACKGROUND: Teriflunomide is an oral disease modifying therapy approved for the treatment of relapsing forms of multiple sclerosis. Teriflunomide' s pharmacokinetics (PK) contribute to its slow elimination, on average taking 6-8 months, though it can take up to 2 years in some instances. This slow elimination can become problematic in certain clinical situations - such as during pregnancy, when teriflunomide has potential teratogenic effects. In such scenarios, an accelerated elimination procedure (AEP) is recommended. Currently, AEPs with oral cholestyramine or activated charcoal are available but are restricted by adverse effects, limited administration routes, and dosing frequencies. METHODS: A single-center, PK interaction study was performed in a total of 14 healthy volunteers, to investigate colestipol hydrochloride (HCl) as an alternative to cholestyramine for the elimination of teriflunomide. Participants received teriflunomide for 14 days, followed by an AEP with colestipol HCl for 15 days. RESULTS AND CONCLUSIONS: The administration of colestipol HCl for 15 days was sufficient to reduce plasma teriflunomide concentrations by greater than 96%. Although colestipol HCl did not completely eliminate teriflunomide with the same effectiveness as cholestyramine, it may offer an alternative method for accelerated elimination of teriflunomide with potentially improved tolerability and more favorable dosing and administration options.

Organic-inorganic hybrid anion exchange hollow fiber membranes: a novel device for drug delivery.

The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) (such as sodium salicylate (NaSA)) for the treatment of chronic arthritis is limited due to the adverse effects and patient non-compliance. In order to solve these problems, anion exchange hollow fiber membranes (AEHFMs) are proposed for the first time here as potential drug carriers. Brominated poly(2,6-dimethyl-1,4-phenylene oxide) (BPPO) is used as the starting membrane material. In-situ sol-gel process of γ-methacryloxypropyl trimethoxysilane (γ-MPS) in BPPO matrix is operated so as to enhance the membranes' thermal and dimensional stability. The performances of the membranes in controlled release of the drug (NaSA as the model drug) are improved accordingly. Loading and release experiments illustrate that the hybrid AEHFM can bind salicylate (SA⁻) at a high loading efficiency (28.4%), and the retention of the drug on the membrane matrix is significantly prolonged (drug released in 7 days under physiological condition: 51.9%, neglecting the drug bound by protein). Meanwhile, the membrane is biocompatible and can support the adherence, growth, and survival of human cells. Overall, the prepared AEHFM is a promising scaffolding material for drug delivery and tissue engineering.

The Bile Acid Sequestrant Acceptability scale validation study.

AIMS: The primary objective of this study was to validate a novel Bile Acid Sequestrant Acceptability (BASA) Scale intended to assess the acceptability and/or tolerability of bile acid sequestrant (BAS) beverage preparations. A secondary objective was to assess the utility of weightings based on subjective clinical importance for the BASA scale individual components and its composite score. METHODS: This was a randomised, single-blind, single site, controlled study of oral administration of 4 g of orange-flavoured generic cholestyramine powder, 12 g of orange-flavoured generic cholestyramine powder and an orange-flavoured sweetened control drink powder, each mixed with water. RESULTS: The study sample included 42 subjects; 26 men and 16 women. Participants were non-Hispanic white (76.2%) or black/African American (23.8%), with a mean age of 51.4 years and body mass index of 30.1 kg/m(2). The components of the BASA scale were taste, texture, appearance and mixability; the possible total BASA scores ranged being 4-20; the higher the BASA scale score, the better the acceptability/tolerability. Composite BASA scale scores were significantly lower for the 4 g (mean BASA score = 10.3) and 12 g (mean BASA score = 9.4) cholestyramine compared with the control drink powder (mean BASA score = 16.7) (p < 0.001). BASA scale scores did not significantly differ between the 4 and 12 g of cholestyramine. (p = 0.215). Weighting of the components did not materially alter the results. Findings for the individual components of the BASA scale were similar to the composite values. CONCLUSION: The BASA scale effectively distinguished between an orange-flavoured BAS powder and a commercial orange-flavour control powder.

Clinical utility of anion gap in deciphering acid-base disorders.

The anion gap (AG) measurement is a very useful tool in the evaluation of patients with acid-base disorders. Once metabolic acidosis is identified, AG will provide the important first step in the differential diagnosis of disorders that either increase the AG and those that leave the AG unchanged. Delta gap is the comparison between change (delta) in the AG and the change (delta) in bicarbonate (HCO(3)(-)). Delta ratio, defined as delta AG:delta HCO(3)(-) is usually 1:1 in patients with an uncomplicated high AG acidosis. A value below 1:1 suggests a combined high and normal AG acidosis. A value above 2:1 suggests a combined metabolic alkalosis and a high AG acidosis. Urine AG (unmeasured anions-unmeasured cations) is an indirect estimate of the urine NH(4)(+) excretion. It is typically negative in patients with normal AG metabolic acidosis secondary to diarrhoea. Utilisation of AG calculations helps clinicians in identifying and treating acid-base disorders.

Beyond cholesterol lowering: pleiotropic effects of bile acid binding resins against cardiovascular disease risk factors in patients with metabolic syndrome.

Prospective epidemiologic studies have shown that dyslipidemia and hyperglycemia are major risk factors for atherosclerotic cardiovascular diseases. Undesirable metabolic conditions are observed to coexist in patients with metabolic syndrome, which is an important risk factor for cardiovascular disease. To prevent cardiovascular disease, a pleiotropic agent is needed to improve the metabolic disorder in patients with metabolic syndrome. Bile acid binding resins increase the fecal excretion of bile acids. The decrease in bile acids returned to the liver leads to an up-regulation of hepatic low-density lipoprotein (LDL) receptor activity, which decreases LDL cholesterol (LDL-C) in the circulation and increases high-density lipoprotein cholesterol. On the other hand, bile acids can also regulate the transcription of genes involved in LDL-C synthesis and cholesterol homeostasis via nuclear hormone receptors. Consequently, these receptors may represent novel therapeutic targets for dyslipidemia and provide insight into the role of the bile acid pathway in other metabolic processes. This review focuses on the recent findings on bile acid binding resins and cardiovascular disease risk factors. Moreover, known and proposed mechanisms of how bile acid binding resins may improve glucose and energy metabolism are discussed; these effects may help to explain the mechanisms by which bile acid binding resins may reduce cardiovascular disease.

Studies on adsorption characteristics of bile acids and methotrexate to a new type of anion-exchange resin, colestimide.

The adsorption characteristics of various bile acids and methotrexate to a new type of anion-exchange resin, colestimide, were studied in vitro and compared with those to cholestyramine. For bile acids, colestimide was shown to have a higher capacity than cholestyramine. For example, approximately 1.4-fold higher for cholic acid and 2.0-fold for deoxycholic acid in water. In the presence of physiological anions, the degree of adsorption of cholic acid to both resins was greatly reduced, whereas adsorption of deoxycholic acid was only slightly reduced. Furthermore, the bed-volume of colestimide swelled about 6.8-fold in water, hence the anion-exchange groups of this resin are expected to be able to function effectively in adsorption of bile acids in the gut. In addition, colestimide was found to have high adsorption capacity for methotrexate, not only in water but also in media containing various physiological anions, and thus it is suggested that colestimide is a potential oral antidote to reduce possible toxicity by methotrexate through interruption of enterohepatic circulation.

[Drug clinics. How I treat various metabolic diseases treated by a drug intervention that targets the intestine]. / Pharma clinics. Comment je traite.... Certaines maladies métaboliques grâce à une intervention pharmacologique ciblée sur l'intestin.

Besides the classical dietary regimen, it is possible to use specific pharmacological approaches, targeted at the intestine, in order to treat some metabolic disorders. Three approaches will be described: anionic resins for treating hypercholesterolaemia, alpha-glucosidase inhibitors for treating diabetes mellitus and reactive hypoglycaemia, and intestinal lipase inhibitors for treating obesity. All these drugs are based on original concepts, but their clinical use is often limited by the occurrence of digestive side-effects. The latter may generally be reduced by progressive and individual titration of the dosage of each drug and/or by following an appropriate diet.

Adverse effects of the treatment for hyperlipidemia.

A variety of treatments to lower elevated plasma lipid levels in patients with hyperlipidemia are available. Adverse side effects ranging from mere annoyances to uncommon serious consequences may be associated with dietary modification, recreational physical exercise, and drug intervention. As in other clinical circumstances, risk-to-benefit ratios must be taken into consideration in the management of hyperlipidemia.