摘要:

The efficacy and safety of pentamidine aerosol versus intravenous cotrimoxazole (trimethoprim-sulfamethoxazole) [TMP/SMX] in the treatment of slight to moderatePneumocystis cariniipneumonia in HIV-infected patients were investigated in a comparative study. The study was designed as an open, randomised, multicentre, prospective study for a collective of 60 patients. Pentamidine aerosol (600 mg/day) was tested against intravenous cotrimoxazole (TMP 20mg/SMX 100mg per kg). Major inclusion criteria were: arterial partial oxygen pressure (pO2) >60mm Hg and forced vital capacity (FVC1) >2L or >50%. 24-hour urine and serum samples were used to evaluate the pharmacokinetics of the tested medications in selected patients. A statistical evaluation was performed according to the ‘intent to treat’ principle after a 4-week follow-up.Case reports of 22 patients treated with pentamidine and 24 treated with TMP/SMX were evaluated. Because of a high frequency of side effects in the TMP/SMX group, the study was discontinued after 46 patients had completed the treatment cycles. However, the response rate in the 2 groups was virtually identical. Complete remission occurred in 16 pentamidine patients and in 10 TMP/SMX patients who received the full course of treatment. In the pentamidine group, 3 patients showed slight side effects; no severe side effects occurred. In the TMP/SMX group, slight side effects were observed in 9 patients, and severe side effects in 7 patients. The difference in the frequency of side effects, the main target variable, was statistically significant (p = 0.0003; 2-tailed, Fisher's exact test; power of comparison = 95%). Treatment success in the absence of side effects was observed in 15 pentamidine patients and in 3 TMP/SMX patients.The study suggests that pentamidine aerosol has advantages over standard intravenous TMP/SMX treatment in slight to moderatePneumocystis cariniipneumonia.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Bioelectrical impedance is a noninvasive method used to determine body composition. Aminoglycosides are broad spectrum antibiotics that have a narrow therapeutic-to-toxic ratio. These agents have traditionally been administered using either population approaches (nomograms or Bayesian methods) or individualised pharmacokinetic monitoring, requiring blood sample analysis. Creatinine clearance is a useful measure of renal function that has been assessed using population approaches or by collecting a 12- to 24-hour urine specimen along with serum creatinine analysis. We investigated the use of bioelectrical impedance to determine predictor equations for the calculation of aminoglycoside pharmacokinetic parameters along with creatinine clearance in 20 noncritically ill patients receiving gentamicin or tobramycin. The bioelectrical impedancederived model was able to explain >70% of the variance for half-life and total volume of distribution of aminoglycosides and >90% of the variance for creatinine clearance. Our model, when compared with a previously published model for gentamicin pharmacokinetic parameters, explained more of the variance for total volume of distribution and total body clearance. Bioelectrical impedance may be a useful tool for aminoglycoside dosing or for the determination of creatinine clearance in noncritically ill patients.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

In order to assess the efficacy and tolerability of mirtazapine (Org 3770), 40 outpatients with a primary diagnosis of anxiety states [International Classification of Diseases (ICD-9)] were treated in a randomised, doubleblind, placebo-controlled, 4-week study (mirtazapine, n = 20; placebo, n = 20). Daily dosages of mirtazapine were 15 to 25mg. The dosage could be titrated upwards or downwards by 5 mg/day, depending on the clinical response or the development of adverse events, respectively. Anxiety symptoms were assessed at baseline and after 7, 14, 21 and 28 days of treatment using the Hamilton Anxiety Scale (HAMAS) and the Zung Anxiety Scale (ZAS); global functioning was assessed by the Global Assessment Scale (GAS). Biochemical, haematological and urinary variables were also measured. After 28 days of treatment, mirtazapine-treated patients experienced significantly greater improvement from baseline in overall anxiety symptoms and psychic anxiety (assessed by HAMAS and ZAS scores) and in global functioning (assessed by GAS scores) than placebo-treated patients. There were no clinically significant changes in biochemical, haematological or urinary variables with either treatment. Mirtazapine was well tolerated; only one patient withdrew from the study because of adverse events. Sedation was experienced significantly more often by mirtazapine-treated patients, while placebo-treated patients complained significantly more often of insomnia and crying, and had more sleep disturbances. In this study, mirtazapine appeared to be an effective and well tolerated treatment for patients with anxiety symptoms as a primary complaint.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The aim of this investigation was to assess the pharmacokinetics and bioavailability of methylergometrine in 6 healthy male volunteers after an oral dose of 0.125mg and after an intravenous dose of 0.200mg. A large variation in bioavailability of between 22 and 136% (mean value 84.9 ± 37.2%) was observed in the 6 volunteers. The lag time was also subject-dependent and ranged between 0.24 and 0.50 hours. After intravenous administration, the pharmacokinetic profile could be described with a 2-compartment model. The distribution half-life (t½&agr;) was 0.19 ± 0.27 hours, the elimination half-life (t½&bgr;) was 1.85 ± 0.28 hours, total body clearance (CL) amounted to 34.1 ± 9.7 L/h, and the steady-state volume of distribution (Vss) was 71.5 ± 25.9L. After oral administration, the pharmacokinetic profile could be described with a 1-compartment model. The absorption half-life (t½abs) was 0.08 ±0.08 hours, and the elimination half-life (t½&bgr;) was 2.08 ± 0.43 hours. This study with oral methylergometrine demonstrated such large interindividual variability in bioavailability that from a pharmacokinetic point of view the oral route of administration does not appear to be the most reliable way for accurate dosing in the prevention of postpartum haemorrhage.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Carboplatin 360 mg/m2was administered intrapleurally to 4 patients with malignant pleural effusion. Simultaneous pleural fluid and plasma samples were collected at various times after treatment to measure the total and filterable levels of platinum. The pleural area under the concentration versus time curve (AUC) for filterable platinum was 26- to 98-fold greater than the corresponding plasma AUC, plasma levels remaining in the range of 3 to 18 μmol/L. The concentrations of platinum in plasma were compared with those observed in 7 additional patients receiving the same dose of carboplatin intravenously. The comparative intrapleural and intravenous therapy led to peak concentrations of platinum 6 to 7 times lower after intrapleural than after intravenous treatment, in significantly lower partial AUCs, and in prolonged levels of filterable platinum following intrapleural treatment. No significant difference, either for total or for filterable platinum, was noted comparing the overall plasma exposure. Systemic clearance and mean residence time values for filterable platinum in plasma were about 1.8 times lower and 2 times higher, respectively, after intrapleural treatment than after intravenous administration. Both the cumulative urinary excretion and renal clearance, as well as the apparent volume of distribution at steady-state for filterable platinum, were comparable with the values obtained after intravenous carboplatin. The observed differences in plasma pharmacokinetics between the 2 routes of administration mainly reflect the delayed absorption of carboplatin into the systemic circulation after intrapleural treatment. The locoregional treatment was well tolerated by all patients, and no symptoms of thoracic discomfort or acute toxicity were noted.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Regular physical activity provokes numerous adaptations in the gastrointestinal tract and liver. It has been suggested that these changes may alter the pharmacokinetics of drugs in humans. We addressed this suggestion by measuring paracetamol pharmacokinetics in a group of healthy young males chosen to represent the widest possible range of habitual physical activity and food intake. Daily caloric intake in the 19 men, obtained from 3-day dietary records, ranged from 1680 to 5110 kcal (21 to 66 kcal/kg). Each volunteer ingested paracetamol 1000mg in the fasted, resting state in the morning; antecubital venous blood samples were analysed for the parent compound and its glucuronide and sulfate conjugates by high-performance liquid chromatography for 6 subsequent hours. We found no evidence that paracetamol pharmacokinetics vary with physical activity or with caloric intake: (a) for the parent compound, there was no correlation in maximum blood concentrations, half-life, total clearance, or area under the curve with individual caloric intake, and (b) when volunteers were divideda prioriinto more active and less active groups, ora posterioriinto higher and lower calorie consumers (a 70% difference in daily caloric intake), these groups had identical plasma disappearance curves for paracetamol itself and for both of its metabolites. We conclude that the enormous variation among humans in long term physical activity and food intake fails to alter any aspect of the appearance or disappearance of paracetamol from blood.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

This double-blind crossover study investigated the efficacy and tolerability of the extended release (ER) form of the calcium antagonist felodipine in 24 patients with mild to moderate primary hypertension using 24-hour ambulatory blood pressure monitoring (ABPM). After a 1-week placebo run-in, patients were randomised to treatment for 1 week with either felodipine ER 5mg or felodipine ER 10mg, both given once daily. At the end of the second week patients were crossed over to the alternative treatment. The 24-hour blood pressure monitoring was performed before randomisation, when on placebo, and at the end of each felodipine ER period. The 5mg dosage reduced supine mean systolic (SBP) and diastolic (DBP) casual blood pressure by 25/11mm Hg and the 10mg dose lowered the pressure by 31/12mm Hg from the placebo period when SBP/DBP was 171/99mm Hg. Both doses of felodipine ER significantly reduced mean 24-hour ABPM supine SBP and DBP compared with placebo. Both day (0600h to 2200h) and night (2200h to 0600h) 24-hour BP profiles showed a significant reduction in SBP and DBP compared with placebo. The trough to peak relationships calculated for both felodipine ER doses from the ABPM were at least 70%. Four patients reported mild vasodilatory adverse events while receiving felodipine ER. In conclusion, analysis of the 24-hour interval indicates that felodipine ER 5 and 10mg once daily is an effective antihypertensive agent that produces a uniform BP reduction that lasts throughout the 24-hour dosage interval.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The objectives of this study were to determine the optimal duration of acid suppression required for the initial treatment of gastric ulcer, and to compare the acid-suppressive effects of omeprazole with the H2-blocker cimetidine in patients with gastric ulcer as determined by 24-hour measurement of intragastric pH. Cimetidine was administered daily to 31 patients, while omeprazole was administered daily to 16 patients and every second day to an additional 16 patients. Ulcers healed within 2 months of treatment in 16 of the 31 patients administered cimetidine. The pH 4 holding time (the proportion of the total 24-hour period of measurement during which intragastric pH was 4 or higher) was 51.9 ± 4.6% of the 24-hour period of measurement for these 16 patients. Patients with unhealed ulcers had significantly shorter durations of ‘pH 4 holding time’ (15.8 ± 2.9% of the 24-hour period). There was no difference in the ‘pH 4 holding time’ of the 24-hour period between those receiving cimetidine who had a curable ulcer within 2 months and those administered omeprazole on alternate days (57.5 ± 7.9%). These findings suggest that obtaining the optimal duration of acid suppression is necessary for the treatment of gastric ulcers. Omeprazole administered as an alternate-day regimen is useful not only for the prevention of recurrence, but also for the initial treatment of gastric ulcer.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The serum levels of copper and zinc were estimated by atomic absorption spectrometry in 7 women with silastic implants releasing norethisterone acetate 140 μg/day. No appreciable change was observed in the circulating concentrations of either of the trace metals after use of the implant for a period of up to 12 months. There was also no change in the serum copper and zinc concentrations during the proliferative and secretory phases of the normal menstrual cycles in 15 women.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS