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Abstract

D. Vitezic and J. Mrsic Pelcic

Clinical Pharmacology Unit, University Hospital Center Rijeka and Department of Pharmacology, University of Rijeka Medical School, Rijeka, Croatia
Erectile dysfunction (ED) (impotence) is a widespread, age-related problem, which affects 52% of men between 40 and 70 years of age. It is classified as psychogenic, organic, or mixed psychogenic and organic. ED is not a problem only of men, because the relationship between partners can also be disturbed. Therefore, adequate treatment of ED is needed and the most convenient and simplest way is oral drug therapy. Sildenafil, phosphodiesterase-(PDE)-5-selective inhibitor has been the drug of choice for patients with ED since it has been launched in March 1998. The results of various studies have confirmed the efficacy of the drug in men with ED of various etiologies, as well as the positive effect of sildenafil on the quality of a partnership. The most frequent adverse effects documented with sildenafil usage are headache, flushes, dyspepsia, visual disturbances and nasal congestion/rhinitis. These adverse effects are dose-related, usually transient and mild, with low withdrawal rate. Several studies performed recently have shown that sildenafil is a safe and effective treatment of ED in patients with cardiovascular disease, who do not take nitrates or nitrate donors concomitantly. Other oral medications for ED include apomorphine, phentolamine, yohimbine, trazodone, testosterone and new PDE-5 inhibitors in Phase III clinical trials, such as vardenafil and tadalafil. It is obvious, according to recent data, that the concept of PDE-5 inhibition has a central position in oral pharmacotherapy of ED. However, larger clinical studies of efficacy and safety should be carried out using most of the other above-mentioned oral agents and these may also gain a place in the therapy of ED. There are no studies directly comparing sildenafil and other treatments of ED or assessing its role in combination with other therapies. According to the present knowledge, the quality of life, not only of patients but also of their sexual partners, will be improved significantly with sildenafil usage and this is an important precondition for overall health of both. Sildenafil is thus a highly effective peroral treatment for ED in patients without contraindications for its use, which can be considered as the first-line therapy with an acceptable risk-benefit ratio.Correspondence to:
Dr. D. Vitezic; Clinical Pharmacology Unit, University Hospital Center Rijeka and Department of Pharmacology, University of Rijeka Medical School, Brace Branchetta 20, HR-51000 Rijeka, Croatia
Email: Dinko.Vitezic@mamed.medri.hr

Abstract

K.-O. Haustein¹, S. Haffner¹ and B.G. Woodcock²

¹Institute for Nicotine Research and Smoking Cessation, Erfurt, and ²Pharmazentrum, University Hospital, Frankfurt am Main, Germany
The data reviewed confirm that mentally ill patients smoke twice as many cigarettes as patients without mental illness. The secretion of neurotransmitters such as noradrenaline, serotonin, dopamine, acetylcholine, g-amino-butyric acid and glutamate is increased by the binding of nicotine to central nicotine receptors. There are also data showing that serotonin formation and secretion in patients with mental illness are influenced by chronic smoking. Cigarette smoke inhibits the activity of monoamine oxidase B, which is responsible for the catabolism of several brain neurotransmitters. Patients suffering from major depression show a comorbidity between heavy smoking and the disease. In patients with schizophrenia treated with neuroleptics, increased cigarette smoking reduces adverse reactions to the drug therapy presumably because of an increase in metabolism of the neuroleptics. There is also evidence suggesting that quitting smoking is more difficult for mentally ill patients than patients without psychiatric disease. Several studies have been carried out on smoking cessation in psychiatric patients. The alternative method of harm reduction, e.g. reducing the number of cigarettes smoked using nicotine patches or chewing gum, is necessary in patients not able to quit. The data indicate that strategies such as the coupling of smoking prohibition with administration of nicotine preparations are useful in smoking cessation. A no-smoking policy in psychiatric clinics, even when this leads to withdrawal symptoms in the patients affected, has no negative effect on mental illness. Because patients with mental diseases are particularly vulnerable to the marketing strategies of the tobacco industry, this chronically ill section of the population requires special protection by the law-makers.Correspondence to:
Prof. Dr. K.-O. Haustein; Institute of Nicotine Research and Smoking Cessation, Johannesstraße 85-87, D-99084 Erfurt, Germany
Email: haustein@inr-online.de

Abstract

N. Schwarz¹, P. Banditt², K.L. Gerlach¹ and F.P. Meyer²

¹Department of Oral and Maxillofacial Surgery, and ²Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany
Objective: If the absorption kinetics of orally administered drugs in preoperative patients are influenced by high anxiety levels as maintained by Simpson and Stakes [1987], then this aspect would have to be taken into consideration in the preparation for surgery and would make dose adjustments necessary in such patients. Methods: We differentiated and quantified the anxiety level in 40 patients, 4 – 5 hours prior to an operation, using the State-Trait Anxiety Inventory (STAI). Subsequently, all patients were given 1000 mg of paracetamol and serum levels were analyzed by means of HPLC. Results: Over the first 3 hours after application there were no significant differences in the parameters Cmax and tmax between patients with high levels of anxiety and patients with low levels of anxiety. However, AUC (area under curve) values were slightly higher in patients with high levels of anxiety. Conclusions: No clinically relevant differences in absorption parameters were observed in patients with high and low levels of anxiety.Correspondence to:
Dr. P. Banditt; Institute of Clinical Pharmacology, University Hospital, Leipziger Straße 44, D–39120 Magdeburg, Germany
Email: peter.banditt@medizin.uni-magdeburg.de

Abstract

A. Boshier¹, N. Pambakian² and S.A.W. Shakir¹

¹Drug Safety Research Unit, Southampton, and ²General Practitioner, London, UK
Sildenafil is a phosphodiesterase-type-5 inhibitor indicated for the treatment of erectile dysfunction in men. We report a case of NAION identified from a cohort of 8,893 patients (from a Prescription-Event Monitoring study) prescribed sildenafil by their primary care physician in England between April and June 1999. This 61-year-old patient had risk factors for NAION independent of drug therapy. It was not possible to be confident about a causal association between sildenafil and NAION, though the possibility could not be ruled out. Epidemiological data suggest that one case of NAION might be expected in a cohort of 8,893 subjects. Thus it remains important for clinicians to consider the range of risk factors for NAION; while equally, the processes of pharmacovigilance need to continue as for any recently launched drug preparation.Correspondence to:
Dr. A. Boshier; Clinical Research Fellow Drug Safety Research Unit, Bursledon Hall, Blundell Lane, Southampton SO31 1AA, UK

Abstract

G. Suarez-Kurtz¹,², F.M. Ribeiro¹, M.C. Salvadori¹ and C.J. Struchiner¹

¹Coordenação de Pesquisa, Instituto Nacional de Câncer, and ²Unidade de Farmacologia Clínica, Santa Casa da Misericórdia, Rio de Janeiro, Brazil
Objectives: To assess the bioequivalence of 2 formulations of carbamazepine and to develop and validate limited sampling strategy (LSS) models for estimating the area under the plasma concentration-time curve (AUC0-¥) and the peak plasma concentration (Cmax) of carbamazepine. Methods: Twenty-four (12 men, 12 women) healthy volunteers received single oral doses (400 mg) of carbamazepine, as reference and test conventional-release formulations, in a standard 2-sequence, 2-period crossover design. Bioequivalence assessment was based on the individual ratios of log-transformed values of AUC0-¥ and Cmax. LSS modeling was developed in a training set of 12 randomly assigned volunteers and was validated on the other 12 subjects (validation set). Results: Carbamazepine AUC0-¥ and Cmax can be accurately predicted (R2 = 0.89 – 0.95, precision = 2.6 – 7.2%) by single-point (72 h) and 2-point LSS models (6, 32 h), respectively. Bioequivalence assessments based on LSS-derived AUC0-¥ and Cmax provided results similar to those obtained using all the concentration-in-plasma data points, and indicated that the 2 formulations are bioequivalent. Conclusion: One- and 2-point LSS models provided accurate estimates of carbamazepine’s AUC0-¥ and Cmax, and allowed correct assessment of bioequivalence between the formulations studied.Correspondence to:
Prof. G. Suarez-Kurtz; Instituto Nacional de Câncer, Coordenação de Pesquisa, Praça da Cruz Vermelha 23/5°, Rio de Janeiro, RJ 20230-130, Brazil
Email: kurtz@inca.org.br

Abstract

K. Nakai¹, M. Fujita² and M. Tomita¹

¹Department of Physiological Chemistry, School of Pharmaceutical Sciences, Showa University, and ²Department of Pharmaceutical Science, National Institute
of Public Health, Tokyo, Japan
Aims: We investigated the comparison of average bioequivalence approach and population approach using bioequivalence study data which have been reported. Materials: On MEDLINE, “bioequivalence” was entered as a key word to search in the 3 journals which were published between 1980 and 1989. Consequently, a total of 17 data sets on AUC and 12 data sets on Cmax were obtained and analyzed in this review. Method: Assessment of average bioequivalence, assessment of population bioequivalence and assessment of inequality of variance (F-test) were conducted after all data were subjected to logarithmic conversion. Results: Of the data sets which were analyzed in this review, 11 data sets on AUC and 3 data sets on Cmax passed the average bioequivalence criterion, and 13 data sets on AUC and 8 data sets on Cmax passed the population bioequivalence criterion. Two data sets on AUC and 1 data set on Cmax passed the average bioequivalence criterion, but not the population bioequivalence criterion. Four data sets on AUC and 6 data sets on Cmax passed the population bioequivalence criterion, but not the average bioequivalence criterion. The correlation coefficient (r) for the population bioequivalence value and difference in the average bioavailability was 0.412, while the correlation coefficient for the population bioequivalence value and the difference in bioavailability variances was 0.708. Conclusions: In this review using bioequivalence study papers which have been reported in references, the episodes to judge that the test formulation is bioequivalent to the reference formulation occurred more predominantly in the population bioequivalence approach than in the average bioequivalence approach, and population bioequivalence approach might be affected more extensively by the bioavailability variance rather than by the average bioavailability.Correspondence to:
Dr. K. Nakai; Pharmaceuticals and Medical Devices Evaluation Center, National Institute of Health Sciences, Ministry of Health, Labor and Welfare, 3-8-21, Toranomon, Minato-ku, Tokyo, Japan
Email: nakai@nihs.go.jp

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Volume 40, No. 9/2002(September)