Bioavailability of two new formulations of paracetamol, compared with three marketed formulations, in healthy volunteers.

The aim of this study was to compare the main pharmacokinetic characteristics of two new paracetamol formulations, powder sachet and tablet, with that of three commercially available paracetamol formulations: two conventional solid tablets and one effervescent tablet. Twelve healthy volunteers participated in an open, single dose (paracetamol 1,000 mg), randomized, five-way, crossover study. Formulations studied included: formulation A: 2 x 500 mg paracetamol tablets (Laboratorios Belmac S.A.); formulation B: 1 x 1,000 mg paracetamol powder sachets (Laboratorios Belmac, S.A.); formulation C: 2 x 500 mg paracetamol film-coated tablets (Panadol, SmithKline Beecham); formulation D: 2 x 500 mg paracetamol tablets (Tylenol, McNeil); and formulation E: 1 x 1,000 mg effervescent paracetamol tablets (Efferalgan, UPSA). The primary variables were area under the plasma concentration time curve extrapolated to infinity (AUC(0-infinity)), maximum plasma concentration (Cmax), and time to maximum plasma concentration (tmax). Mean AUC(0-infinity) ranged from 52.6 (B) to 56.3 microg x h/ml (D); mean Cmax varied between 17.98 (C) and 20.73 microg/ml (E); mean tmax ranged from 0.40 (E) to 0.88 h (C); and median t(1/2) varied between 2.65 (C) and 2.81 h (A). Formulations A, B and E showed significantly shorter tmax than formulation C. The tmax and Cmax values found for formulations A and B were very similar to that found for E, an effervescent tablet formulation. In conclusion, the two new formulations of paracetamol tested in this study were absorbed rapidly after a single oral dose in healthy volunteers, similar to an effervescent paracetamol formulation and significantly faster than two ordinary commercialized paracetamol tablets.

The clinical uroselectivity of alfuzosin is not significantly affected by the age of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVE: To assess the effect of the age of patients with benign prostatic hyperplasia (BPH) on the clinical uroselectivity of alfuzosin during general medical practice. PATIENTS AND METHODS: The present national, multicentre, open-labelled, observational study involved 4018 Spanish outpatients with BPH, i.e. showing lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction. The patients received sustained release (SR) alfuzosin, 5 mg twice daily, for 2 months. The primary efficacy criteria were symptomatic improvements, as assessed by the International Prostate Symptom Score (IPSS) and quality of life (QoL) index. Safety was assessed by monitoring cardiovascular data and adverse events. RESULTS: The patients were divided into four age groups, i.e. < 56, 56-65, 66-75 and > 75 years. All groups of patients showed a mean IPSS decrease of 11-12 (55.8-65.4% from baseline) at the end of the study, while the QoL decreased by 2-3 points (55.6-63.6% from baseline). There were no relevant effects of age on the efficacy of the treatment. Moreover, alfuzosin was well tolerated independently of the age of the patient; 1.2% of the patients enrolled withdrew because of adverse events. The qualitative distribution of vasodilatory/nonvasodilatory adverse events was similar in all age groups. The incidence of asymptomatic orthostatic hypotension was low (0.58%) and not affected by the age of the patients. CONCLUSION: This study confirms that the clinical uro-selectivity of SR-alfuzosin, already described in ran-domized controlled studies, is not significantly affected in clinical practice by the age of the patients. This is considered particularly relevant to the characteristics of patients with BPH, as they are mostly elderly men.

Age-stratified analysis of I-PSS and QoL values in spanish patients with symptoms potentially related to BPH.

OBJECTIVE: The main goal of the present study was to determine age-related symptom changes using a validated Spanish International Prostate Symptom Score (I-PSS) and quality of life index (QoL) in Spanish patients with symptomatic benign prostatic hyperplasia (BPH). METHODS: A total of 2,875 patients with the clinical diagnosis of symptomatic BPH were evaluated. Data were collected during current medical practice in a national study. Patients were excluded if they had any previous prostate operation or suspicion of prostate cancer. I-PSS was self-administered and compared with the physician's global impression. RESULTS: I-PSS symptoms, both voiding and storage symptoms, increased significantly with age (p<0.0001) as well as QoL (p<0.0017). A change in the I-PSS categories (minor, moderate and severe) was found with age, increasing severe symptomatic patients in the oldest groups. A significant correlation was found between I-PSS and QoL (r = 0.49, p<0.001), being this relationship linear and not significantly influenced by age. CONCLUSIONS: This study confirms reliable results using a validated Spanish I-PSS in a large national representative sample of Spanish patients with BPH symptoms. The age-stratified analysis showed that the natural progression of BPH with age was related to an increased symptomatology and bothersomeness, well reflected by increases in the I-PSS and QoL values. Nevertheless, the effect of symptomatology on quality of life was not strongly influenced by the age of the patient.

Safety and efficacy of sustained-release alfuzosin on lower urinary tract symptoms suggestive of benign prostatic hyperplasia in 3,095 Spanish patients evaluated during general practice.

OBJECTIVES: This general practitioner-run study assess the security as well as the efficacy and impact on health-related quality of life of a sustained-release (SR) form of alfuzosin in Spanish patients suffering from lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: 3,095 patients with symptomatic BPH were enrolled into a national, multicentric, open, phase IV observational study. The period of active treatment studied (5 mg, twice daily) was 60 days. Safety was assessed by monitoring blood pressure and spontaneous adverse events. Symptoms were assessed using a validated Spanish International Prostate Symptom Score (I-PSS). Impact of symptoms on health-related quality of life was assessed using the quality of life index (L). RESULTS: 101 adverse events were reported in 82 patients (2.6%). 28 adverse events (2.6%) were classified as severe. 49 patients (1.6%) dropped out of the study due to adverse events but only 17 of these patients (0.5%) showed adverse events related to vasodilation. Incidence of postural events (vertigo, postural hypotension/hypotension, headache and dizziness) was low (55 patients, 1.8%) and effects on sexual function were found not significant: no retrograde ejaculation was reported and only 1 patient (0.03%) showed impotence. Blood pressure or heart rate showed no clinically significant changes. All the I-PSS scores decreased significantly during the treatment with alfuzosin, improvement being excellent in 60% of the patients. Symptomatic improvement was associated with a significant improvement in health-related quality of life. CONCLUSIONS: This large study conducted during general practice on Spanish BPH patients confirms the efficacy on LUTS and good safety profile of SR alfuzosin, especially its low incidence of postural symptoms and no deleterious effect on sexual function.