Fostering Competence in Medicines Development: The IFAPP Perspective.

IFAPP (International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine) is a nonprofit organization with the mission to promote Pharmaceutical Medicine & Medicines Development (PM&MD) by enhancing the competencies and maintaining high research ethical standards of Pharmaceutical Physicians and other professionals involved in medicines development worldwide, leading to the availability and appropriate use of medicines for the benefit of patients and society. About 30 national professional associations related to PM&MD, involving 7000 professionals, are affiliated to IFAPP. Medicines development has traditionally been a challenging enterprise, with high risk, high investment, and potentially high returns in the lengthy and complex process of identifying a new chemical entity as a candidate for development and possibly succeeding in bringing it as a pharmaceutical product to the market.

Corrigendum: Core competencies for pharmaceutical physicians and drug development scientists.

[This corrects the article on p. 105 in vol. 4, PMID: 23986704.

Core competencies for pharmaceutical physicians and drug development scientists.

Professional groups, such as IFAPP (International Federation of Pharmaceutical Physicians and Pharmaceutical Medicine), are expected to produce the defined core competencies to orient the discipline and the academic programs for the development of future competent professionals and to advance the profession. On the other hand, PharmaTrain, an Innovative Medicines Initiative project, has become the largest public-private partnership in biomedicine in the European Continent and aims to provide postgraduate courses that are designed to meet the needs of professionals working in medicines development. A working group was formed within IFAPP including representatives from PharmaTrain, academic institutions and national member associations, with special interest and experience on Quality Improvement through education.

Actovegin®: a biological drug for more than 5 decades.

Actovegin(®) is a biological drug manufactured from a natural source: it is a calf blood hemodialysate. Its therapeutic benefits stem from a variety of pharmacodynamic actions that can be summarized to a common goal, i.e.

Oral terbinafine (Lamisil) in the short-term treatment of fungal infections of the skin: results of a post-marketing surveillance study.

Oral terbinafine (Lamisil, Novartis Pharma AG, Basel, Switzerland) is an effective therapy for fungal infections of the skin and nails. A post-marketing surveillance study was undertaken to evaluate the clinical efficacy and safety of oral terbinafine. A total of 454 patients with clinically and mycologically confirmed superficial fungal infections of the skin were enrolled from 79 dermatology clinics.

Benazepril, an angiotensin converting enzyme inhibitor: drug interaction with salbutamol and bronchial response to histamine in normal subjects.

Aims: To investigate the effect of the angiotensin converting enzyme inhibitor, benazepril, on pulmonary function.

Methods: We investigated the influence of benazepril, on lung function and the interaction with inhaled salbutamol (0.1 to 6.

Disposition of [14C]pinacidil in humans.

Pinacidil [(+/-)-2-cyano-1-(4-pyridyl)-3-(1,2,2-trimethylpropyl)guanidine monohydrate] is a novel, direct-acting vasodilator antihypertensive agent. The cyano 14C-labeled drug is rapidly and completely absorbed after an oral 12.5-mg dose in solution.

Adaptation of electrolyte transport in rat large intestine after proximal resection. II. Colon after 50% jejunoilectomy combined with cecectomy.

Electrolyte transport was studied in rat colon adapting to 50% small intestinal resection with cecectomy. Four weeks after surgery, colonic gross surface area, dry and wet weight were increased compared to sham-operated controls. Net absorption in vivo of sodium, chloride and volume was stimulated per organ and per unit tissue mass, and net potassium secretion was diminished.

Mechanism of action of diphenolic laxatives: the role of adenylate cyclase and mucosal permeability.

Net fluid movement and mucosal 14C-erythritol clearance were measured in ligated colonic loops of the rat in vivo. The diphenolic laxatives, oxyphenisatin and bisacodyl, dose-dependently inhibited net fluid absorption or caused secretion, both increased the 14C-erythritol clearance. Pretreatment with the adenylate cyclase inhibitor, RMI 12 330 A, did not change these results.

Differentiation of secretagogue drugs by chlorpromazine in rat intestine in vivo.

The effect of chlorpromazine (CPZ) on passive epithelial permeability and net fluid movement induced by secretagogues was tested in the rat intestine in vivo. CPZ, in a dose of 20 mg/kg intramuscularly, did not alter colonic permeability either in control conditions or during increased permeability caused by deoxycholic acid (DOC) or bisacodyl. Fluid secretion induced by cholera toxin and theophylline was strongly reduced by CPZ.

Influence of vasopressin and calcium on electrolyte transport across isolated colonic mucosa of the rat.

Vasopressin enhanced the absorption of water and Na+ across everted sacs of rat colon descendens but had no effect on absorption across the colon ascendens. The short-circuit current (Isc) and open-circuit potential difference (p.d.

Effect of deoxycholate on the perfused rat colon. Concentration dependence of the effect on net fluid and electrolyte transfer and the correlation with paracellular permeability.

We reexamined the question whether the deoxycholate-evoked alteration of net transfer of fluid and electrolytes is primarily caused by active secretion or paracellular filtration. In the in vivo perfused rat colon, deoxycholate caused a dose-related increase in 51Cr-EDTA clearance proportional to the rate of fluid, sodium, and chloride secretion. These increases of fluid production and epithelial permeability were reversible and showed the same time dependence.

Is the secretagogue effect of deoxycholic acid mediated by the adenylate cyclase-cAMP system.

The role of the adenylate cyclase (Ac)-cAMP system in mediating deoxycholic acid (DOC)-induced fluid secretion was studied in the rat jejunum and colon in vivo using the AC inhibitor, RMI 12 330 A. A potent inhibitory effect of RMI 12 330 A on fluid secretion induced by cholera toxin was demonstrated in ligated rat jejunal loops. On the contrary, the changes of fluid movement in jejunal and colonic loops caused by DOC could not be influenced by RMI 12 330 A, and mucosal cAMP levels of colonic loops were not increased.

Independence of the activation of mucus and potassium secretion on the inhibition of sodium and water absorption by deoxycholate in rat colon.

The dose dependence of the influence of deoxycholic acid (DOC) on fluid and sodium absorption, transmural potential difference (PD), permeability of 14C-erythritol and secretion of potassium and mucus (protein bound hexoses) was measured in the in vivo perfused rat colon. The following results were obtained: 1. The threshold concentration for the inhibitory effect of DOC on fluid and sodium absorption is 2 mmol.

Pharmacodynamics of human insulin (recombinant DNA)--regular, NPH, and mixtures--obtained by the Gerritzen method in healthy volunteers.

The study was concerned with the comparison of the action profile of regular and NPH preparations of human insulin (recombinant DNA) and of PPI (pork purified insulin). In addition, the action profiles of some mixtures (10:90, 15:85, 20:80, 25:75, 30:70) of regular and NPH human insulin were evaluated. The comparisons were based on the Gerritzen test.

Effect of deoxycholate on the perfused rat colon. Scanning and transmission electron microscopic study of the morphological alterations occurring during the secretagogue action of deoxycholate.

In parallel with the study on the correlation between increased mucosal permeability and the secretagogue effect of deoxycholate on the perfused rat colon, we examined the mucosal morphology by scanning and transmission electron microscopy. Dependent on concentration (2, 4, and 8 mmol/l), the treated mucosa showed structurally altered 'ballooned' absorptive cells, severely injured sloughing cells, and exfoliated cells lying on the surface. In spite of these changes, the continuity of the epithelial lining was maintained.

Movement of thallium (I) ions in vitro.

1. Movement of thallium (I) ions across the mucosal epithelium of descending rat colon, stripped of the muscularis externa in vitro was determined under voltage clamp conditions. 2.

The short-circuited everted sac of rat colon mucosa.

A short-circuited preparation of everted rat colon sacs is described. The serosal current electrode is a AgAgCl wire. A cylindrical agar bridge or AgAgCl electrode may be employed on the mucosal side.

Effect of diphenolic laxatives on Na+-K+-activated ATPase and cyclic nucleotide content of rat colon mucosa in vivo.

1. The effect of bisacodyl and oxyphenisation on the Na+-K+- and Mg2+-activated ATPase and on the mucosa levels of cAMP and cGMP was investigated in transporting ligated loops of the rat colon in acute studies and in chronic feeding experiments 2. The specific activity of the Na+-K+-ATPase was lowered in both types of experiments, concomitantly with a reduction in net sodium absorption.

Comparative study of the effect of cholera toxin and sodium deoxycholate on the paracellular permeability and on net fluid and electrolyte transfer in the rat colon.

1. The effect of deoxycholate and cholera toxin on the transfer of water, sodium, potassium and chloride and on mucosal permeability was studied in perfusion experiments on rat colon in vivo. The influence of both secretagogues on surface morphology was assessed by scanning electron microscopy.

Influence of hydrostatic pressure gradients on net transfer of sodium and water across isolated rat colonic mucosa.

1. The dependence of net transfer of water and sodium on hydrostatic pressure gradients from the serosal to the mucosal side was investigated in everted sacs of the stripped mucosa of the rat colon. 2.

Transfer of sodium and water through isolated rat colonic mucosa under the influence of deoxycholate and oxyphenisatin.

1. The influence of oxyphenisatin (OP), a diphenolic laxative, and deoxycholate (DC) on the transfer of sodium and water in an everted sac preparation of stripped rat colon was investigated. 2.

Pathway of sodium moving from blood to intestinal lumen under the influence of oxyphenisatin and deoxycholate.

The transfer of (51)CrEDTA and inulin--substances which are distributed only in the extracellular space--across the rat colonic mucosa in vivo is increased by oxyphenisatin O (3.5 times 10(-5)M) and deoxycholate D(3 times 10(-3)M). O and D do not change the size of the intra- and extracellular fluid compartments of the mucosa as measured with (51)CrEDTA from the blood side.