International journal of clinical pharmacology, therapy, and toxicology最新文献

A prospective, controlled, double-blind, double-dummy, multicenter clinical trial was made to assess the efficacy and tolerability of iron-protein-succinylate (ITF 282) in comparison with a well known iron preparation in the treatment of iron deficiency or iron deficient anemia. One thousand and ninety-five patients affected with iron deficiency or overt iron deficient anemia were randomized to receive either two ITF 282 tablets/day (60 mg iron each) or a commercially available ferrous sulphate controlled release tablet (one tablet containing 105 mg iron/day). Five hundred and forty-nine patients received ITF 282; 546 patients were treated with ferrous sulphate. Both treatments lasted 60 days. The treatment outcome was checked by evaluating special hematology, symptomatology, safety hematology and hematochemistry. After two months of treatment, the normalization of the main hematologic parameters in both groups was detected. Although in the first month the reference treatment appears to provide somewhat faster results, at the end of the observation, the values of hematocrit, hemoglobin and ferritin were greater in the ITF 282 group, indicating a more progressive and steady therapeutic effect. The overall clinical rating was significantly in favor of ITF 282, with 78.9% of favorable results vs 67.6%. By dividing the patient population according to pathological conditions (iron deficiency or overt anemia), or according to the etiopathogenesis of the iron deficiency (increased requirement, or increased loss in adults and in the elderly), separate analyses on the treatment outcome were made (and have been included). The general tolerability, although favorable with both treatments, was significantly more favorable with ITF 282. With this medication, 63 patients (11.5%) complained of 69 adverse reactions (25 heartburn, 19 constipation, 25 abdominal pain) vs 141 events reported by 127 patients (26.3%) with the reference medication (33 heartburn, 31 epigastric pain, 23 constipation, 32 abdominal pain, 8 skin rash, 14 nausea). These observations confirm that, although the most modern preparations of ferrous sulphate exhibit a relatively low frequency of adverse events of limited clinical concern, it is nevertheless possible to decrease both the prevalence and the duration of such events without prejudice for the clinical efficacy, with the use of more "physiological" preparations in which the iron is reversibly bound to a protein carrier, thus effectively removing one of the main obstacles to the correct compliance with treatments that must be administered for prolonged periods of time.

An intensive and prospective surveillance study of 54 patients hospitalized in the Internal Medicine Unit of Clinical Hospital of the Catholic University of Chile, who required heparin in the period between June and December of 1991 was done. The aim of the work was to characterize and study the incidence of the adverse reactions associated with heparin therapy, with special emphasis on abnormal serum transaminase elevation. Abnormal transaminase elevation was defined as a rise over 20% of the serum transaminase baseline value. For determining the serum transaminase level, a UV spectrophotometric method was used. The incidence of the adverse drug reactions (ADR) was 24.1% (13 ADR), 8 of which (14.8%) were related with heparin therapy. Three of them (5.5%) corresponded to alanine transaminase (ALAT) increase and five (9.3%) to aspartate transaminase (ASAT) elevation. By means of global introspection method, 3 cases of ALAT increases were defined as probable and 6 as possible, while 5 ASAT increases were estimated as probable and 14 as possible. All of them were of slow onset, did not require treatment and hospital stay was not prolonged. Two patients' characteristics--age and sex--were associated with the development of heparin-induced abnormal alanine transaminase concentrations. The younger male patients showed a greater frequency of heparin-induced ALAT elevation. However, this association was not observed with the heparin-induced ASAT increase. These reactions were dose-dependent. Patients with heparin-induced ALAT elevation received a dose of 154,220 IU +/- 72,970 IU in comparison to patients without that adverse reaction who received 96,210 IU +/- 40,340 IU. This difference was statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibiotics of the beta-lactam class may cause coagulation defects and bleeding. It has been suggested that N-methyltetrazolethiol (NMTT), a common side chain group at the 3'-position of the cephem or 1-oxacephem frame, could be responsible for the hypoprothrombinemic effect of the antibiotics and that it could inhibit the liver vitamin K-epoxide reductase activity. Flomoxef (6315-S) is a new oxacephem antibiotic which differs from latamoxef because it has [1-(2-hydroxethyl)-1H-tetrazol-5-yl] thiomethyl (HTT) as a side chain at the 3'-position of cephem group instead of NMTT and an extensive modification of 7 beta-acylamino side chain. The present study was carried out to study its effects on vitamin K-dependent blood coagulation parameters in human volunteers. Ten adult patients (6 men and 4 women), suffering from chronic bronchitis, entered into the study. Each patient received ten 1 g i.m. injections of flomoxef at 12-hourly intervals. Apparently, the treatment with this oxacephem antibiotic had no significant effect. PT, PTT and fibrinogen remained in the normal range in all patients and factors II+VII+X, protein C, protein S and AT III were not depleted. The trend was similar both in men and women. Based on the results of the present study, we conclude that flomoxef is an antibiotic that does not exhibit an effect on blood coagulation, even in males.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum concentrations for zinc and copper were determined in epileptic patients who had undergone one month of therapy with a mono-antiepileptic drug (mono-AED) (carbamazepine, CBZ; phenobarbital, PB; phenytoin, PHT; valproic acid, VPA). There were 114 epileptic patients and 30 healthy volunteers who participated in this study. Although zinc concentrations tended to decrease, there were significant increases in copper concentrations in patients who were treated with mono-AED (CBZ, 32.9%; PB, 36.4%; PHT, 39.0%; VPA, 25.4%) when compared with healthy volunteers. There was no significant change in either zinc or copper concentrations among the four mono-AED groups. No dose-related changes could be observed either for zinc or copper concentrations. In conclusion, this study demonstrated that both zinc and copper concentrations in epileptic patients under chronic AED therapy differed somewhat from the control level, but remained within the normal range, indicating that there is no need to adjust serum concentrations of either of these trace elements in order to treat diseases related to them.

Intranasal verapamil administration may limit intrasubject variability encountered due to the metabolism differences of the d and l-isomers. We simultaneously measured verapamil/norverapamil concentrations, PR interval, heart rate (HR), and mean arterial pressure (MAP) in six healthy volunteers receiving verapamil 5 mg intranasally and intravenously on two separate occasions. Two subjects achieved measurable verapamil concentrations after intranasal administration with a mean bioavailability of 16.1%. Intranasal bioavailability was limited secondary to instillation volume. No relationship between HR, MAP and verapamil concentration was noted. A relationship between mean intravenous verapamil concentration and mean PR interval was observed; however, extensive interpatient variability existed: two subjects demonstrated enough counterclockwise hysteresis to skew mean data. Mean data may falsely represent the verapamil concentration-effect relationship. Intranasal verapamil administration is limited by instillation volume. Development of a concentrated dosage form is necessary to assess bioavailability. Concentration-effect relationships are more accurately described using individual, rather than mean data.

We retrospectively studied 2,695 patients admitted to the Department of Medicine over a 10-month period in 1990 to determine the incidence of drug-related hospitalization. A drug-related problem was identified as the primary cause of hospitalization in 109 (4.0%) admissions. The incidence was significantly greater in the elderly group as compared with the non-elderly group (5.2% vs 3.2%). Non-steroidal anti-inflammatory drugs, hypoglycemic agents, herbal medicine, adrenocorticosteroids and antihypertensive drugs were most often involved. The five most common adverse events were upper gastrointestinal tract bleeding, skin rashes, hypoglycemia, hypercorticism and hepatitis. Iatrogenic disease was fatal in 2 cases. Patients used drugs without medical supervision in 45 cases. In view of the increasing complexity of modern pharmacotherapy and the popularity of self-medication in our society, educational efforts should be enhanced for medical professionals and the general population to reduce the risk of drug-related hospitalization.

A malignant pheochromocytoma with several unique features was studied. Initially, its histological and catecholamine secretory properties and physiological effects were terminated by an infarct prior to its excision in 1973. However, in 1985 a metastasis was resected from the right atrium. Hypertensive crisis during surgery was controlled by the administration of phentolamine but not by nitroprusside. Within 2 months, it was again detected at this same site. Biochemical studies confirmed its recurrence. The tumor did not respond to chemotherapy with vincristine, cyclophosphamide and dacarbazine, but there has been physiological and biochemical improvement from inhibiting catecholamine biosynthesis with metyrosine. We recommend that both phentolamine and sodium nitroprusside be readily available during resection of a pheochromocytoma.

A comparative bioavailability study was carried out on two enteric-coated capsules (20 mg each) of omeprazole (omeprazole, Alembic: "A" and Losec, Astra, England: "B"). The in-vitro dissolution of both products "A" and "B" met the prescribed USP standard. The bioavailability of single dose (20 mg) and multiple doses (20 mg once daily for 7 days) of both products "A" and "B" were carried out in eight healthy male volunteers in a crossover design. The rate and extent of bioavailability of omeprazole was higher in product "A" following a single oral dose, suggesting its therapeutic advantage over the product "B" in the prevention of acid aspiration during surgery. In multiple dose study, the two products were found bioequivalent as assessed by AUC0-infinity, Cmax, tmax and t1/2 elimination.

The aim of the study was to investigate the extent of prescription drugs administered for common disorders during the post partum period. This is a prospective survey of disorders and drug use in 1) immediate postpartum mothers (n = 200) admitted to the maternity wards, 2) in post-natal hospital follow-up clinic (n = 200) and in 3) the rural home based community (n = 100). A pretested questionnaire was filled in by medical officers after interviewing the mothers. The mean age of the mothers was 25 years and a literacy rate of 50% above the 10th grade. Over 80% of the women were multigravida in the entire sample; 45% underwent Caesarean Section in a hospital; 97.6% had a normal delivery in the community. In the hospital settings 4.1% infants had jaundice and 1% had congenital anomalies. In the community setting, diarrhoea and pneumonia was seen in 2.6% of the infants. Apart from the use of nutritional supplements, such as iron, calcium, multivitamins etc., most commonly prescribed drugs were analgesics (in 70% of patients in the hospital settings, 56% of the patients in the postnatal clinic and 37.6% patients in the community), and antibiotics (90% of the patients in the hospital settings, 86% of the patients in the postnatal clinic and 13% of the community based patients). Antihypertensives agents (2.5% of the patients), digoxin (1.5% of the patients), bronchodilators (1% of the patients) and sedatives (3.5% of the patients) were prescribed to admitted patients.(ABSTRACT TRUNCATED AT 250 WORDS)

For about 6 years after the marketing of oral formulations of fosfomycin calcium (FOM-Ca) in December, 1980, we collected the data on 35,481 cases and analyzed it regarding safety. Primary side-effects consisted mainly in gastrointestinal disturbances, damage to skin and adnexa, liver and bile duct disorders. Specifically, diarrhea, nausea, abdominal pain, anorexia, eruption and increased serum transaminase were frequent. Serious and newly detected side-effects after marketing were pseudomembranous colitis and melena, one case each. As for the oral administration of FOM-Ca to 83 patients hypertensive to beta-lactams, gastrointestinal side-effects were seen but none of them developed hypersensitivity, an allergic reaction.