International journal of clinical pharmacology research最新文献

In this pilot, randomized, double-blind study, we compared the effects of policosanol and lovastatin on lipid profile and lipid peroxidation in patients with dyslipidemia and type 2 diabetes mellitus. After 4 weeks on a cholesterol-lowering diet, 36 patients were randomized to policosanol (10 mg/day) or lovastatin (20 mg/day) tablets o.i.d. for 8 weeks. Policosanol significantly (p < 0.001) lowered serum low-density lipoprotein-cholesterol (LDL-C) (29.9%), total cholesterol (21.1%), triglycerides (13.6%) and the LDL-C/high-density lipoprotein-cholesterol (HDL-C) (36.7%) and total cholesterol/HDL-C (28.9%) ratios and significantly (p < 0.01) increased HDL-C (12.5%). Lovastatin significantly (p < 0.001) lowered LDL-C (25%), total cholesterol (18%), triglycerides (10.9%) and the LDL-C/HDL-C (30.4%) and total cholesterol/HDL-C ratios (23.9%) and significantly (p < 0.01) raised HDL-C (8.3%). Policosanol was more effective (p < 0.05) than lovastatin in reducing both ratios and in increasing (p < 0.05) HDL-C. Policosanol, but not lovastatin, significantly raised the lag time (20.9%) of Cu+2-induced LDL peroxidation and total plasma antioxidant activity (24.2%) (p < 0.05). Both policosanol and lovastatin significantly decreased the propagation rate (41.9% and 41.6% respectively, p < 0.001), maximal diene production (8.3% and 5.7%) and plasma levels of thiobarbituric acid reactive substances (9.7% and 11.5%, p < 0.001). Both treatments were well tolerated. Only one patient in the lovastatin group withdrew from the trial due to adverse events. In conclusion, policosanol and lovastatin administered short term to patients with dyslipidemia secondary to type 2 diabetes were effective in lowering cholesterol and in inhibiting the extent of lipid peroxidation. Policosanol (10 mg/day) was slightly more effective than lovastatin (20 mg/day) in reducing the LDL-C/HDL-C and total cholesterol/HDL-C ratios, in increasing HDL-C levels and in preventing LDL oxidation. Nevertheless, since this was a pilot study, further clinical studies performed in larger sample sizes of diabetic patients are needed for definitive conclusions.

This study reports nurses' perceptions of medication errors and of their appropriate reporting. Thirty-three percent of the participants believed the main cause of medication errors was nurses' tiredness or exhaustion, while 30% of participants indicated that the main cause was the poor legibility or illegibility of physcians' writing on the doctor's order form. Some medication errors were not reported because nurses were afraid of reprisals (63%).

Preliminary feedback from physicians and pharmacists in Trinidad suggests that generic pressurized metered dose inhalers (pMDIs) of salbutamol are not as effective as Ventolin and that they have poor patient acceptance. This study was designed to compare the clinical efficacy and tolerance of two generic inhalers available in Trinidad (Asthalin and Salomol) with Ventolin in stable asthmatics. Twenty-one physician-diagnosed stable asthmatics were administered the inhalers in a Latin-square randomized double-blind study with 80% power to identify differences in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) before and 0.25, 0.5, 1, 2 and 3 h after inhalation. Pulse and blood pressure were recorded at similar time points. Seventeen patients completed the study. Within 15 min basal respiratory function significantly increased following inhalation from all three inhalers with a gradual decline over the observation period. Asthalin produced the highest changes in FEV1, PEFR and the longest duration of effect (p < 0.001). Respiratory function tests did not differ between Ventolin and Salomol. Pulse was not affected by treatments and mean arterial blood pressure fell after Asthalin. Ventolin was not superior to the generic pMDIs in improving pulmonary function. Fifteen patents reported cough sensation after Asthalin. Throat irritation and cough sensation after inhaling Asthalin may negate patient compliance. We suggest that optimizing particle size and cascade impact in the Asthalin inhaler may improve patient tolerance and acceptance with enhanced treatment outcome with cost-efficacy.

Calcific periarticular disease is characterized by the deposition of calcium phosphate crystals in many tendons and particularly in the rotator cuff tendons. Calcifications of any size may be accompanied by painful shoulder syndrome and tendon tears. Ecographic assessment of changes in the size of calcifications may be a marker of tissue changes in evolving shoulder periarthropathies. The aim of this study was to compare variations in pain and ultrasound dimensions in the calcifications in the tendons of the rotator cuff in patients treated with disodium-clodronate compared with those treated with paracetamol and nimesulide. In all groups, pain reduction occurred over a 6-month period, but was significantly greater in patients administered disodium-clodronate than in those administered nimesulide or paracetamol. A significant reduction in the size of calcifications was also observed in all three groups, but this reduction was more marked in the disodium-clodronate group.

Ursodeoxycholic acid (UDCA) is currently used for the treatment of cholestatic liver disease and for cholesterol gallstone dissolution. Various formulations have been designed to enhance its intestinal absorption or to improve patient compliance through once-a-day administration. The pharmacokinetics and bioavailability of four commercially available modified-release UDCA formulations (450 mg) were studied in 12 healthy subjects randomly receiving the four drugs under study. Serum samples were collected hourly for a 12-h period after administration and UDCA concentrations were measured using a specific enzyme immunoassay. For each formulation, Cmax, tmax, and the area under the curve (AUC) were determined and compared. Although all formulations were designed to provide sustained release, we observed different pharmacokinetics among the studied formulations. One of the formulations (sustained-release ursodeoxycholic acid Ratiopharm 450 mg tablets) showed high bioavailability, but failed to produce sustained release. In contrast, two other formulations (modified-release ursodeoxycholic acid Dorom 450 mg capsules and controlled-release Ursobil HT 450 mg capsules) provided sustained release, but did not offer efficient bioavailability. A fourth formulation (Ursilon retard 450 mg) exhibited gradual UDCA release lasting over 10 h, with efficient bioavailability, similar to that of conventional prompt-release formulations administered at the same dose. These data highlight the variability of commercially available sustained-release formulations. Manufacturers should be encouraged to provide drug kinetics and bioavailability data to further support the claimed pharmacokinetics.

We investigated the effects of extracts from the dried flower of Pueraria thomsonii on blood ethanol and acetaldehyde levels in humans consuming alcoholic beverages. The extracts of Pueraria thomsonii had no influence on blood ethanol and acetaldehyde concentration in humans. However, the extracts increased the elimination rate constant of blood acetaldehyde, although they had no effect on the elimination of blood ethanol in humans. These results suggest that Pueraria thomsonii promotes the elimination of blood acetaldehyde in humans. The present study clinically suggests that a modest stimulatory effect of Pueraria thomsonii on the elimination of blood acetaldehyde may passively mitigate acetaldehyde toxicity, such as flushing, palpitation, headache, etc., associated with excessive alcohol intake.

The aim of the present study was to compare the efficacy and tolerability of a new form of nonsteroidal antiinflammatory drug (NSAID), acematacin (Acemet), with indomethacin, in patients suffering from osteoarthritis (OA). Patients diagnosed with OA were included in a double-blind, randomized, controlled parallel group study A total of 42 patients were randomized to either acemetacin 60 mg t.i.d. or indomethacin 25 mg t.i.d. for 28 days. At an outpatient clinic, each patient was followed up regularly for efficacy, compliance and possible adverse events. Both drugs produced a statistically significant improvement for primary efficacy variables: change of pain score during motion and restriction of body movement. Values for overall tolerability and incidence of gastrointestinal side effects were significantly lower for acemetacin than for indomethacin. We therefore suggest that acemetacin, by demonstrating significant tolerability and safety advantages, is as effective as indomethacin for the treatment of OA.

Some investigators have postulated that a constant low blood level might be the ideal mode of treatment, while others have seen no reason to divide up the daily dose. To our knowledge, this study is the first to include crossover of subjects to eradicate individual differences. Our aim was to compare the pharmacokinetic effects of administering etoposide three times a day vs. once a day as 25 mg capsules. Two groups of four patients each received 75 mg/day oral etoposide for 2 days either as 75 mg once daily, or as 25 mg three times daily for 2 days. On days 8 and 9, the treatments were switched between groups. On the one-dose schedule, Cpeek (peak plasma concentration) was greater than 2 micrograms/ml in five patients and greater than 3 micrograms/ml in three patients, while in none of the patients on the three-dose schedule did the peak exceed 2 micrograms/ml. No significant difference was found in terms of Cmean (calculated by dividing the area under the curve by the observed time) between the two treatments. Variability of blood concentrations of etoposide over a 24 h period was high on the one-dose schedule (median 95%, range 54-148%) but it was lower on the three-dose schedule (median 39%, range 28%-55%). No significant differences were found between the two different dosing schedules in terms of the median duration of etoposide blood levels above 0.5 microgram/ml and above 1.0 microgram/ml. These results suggest that detailed clinical toxicity and efficacy data are needed to clarify the possible benefits of the fractionated administration of oral etoposide.