Omeprazole, azithromycin and amoxicillin or amoxicillin plus clavulanic acid in eradication of Helicobacter pylori in duodenal ulcer disease

Treatment with omeprazole (OME), azithromycin (AZI) and amoxicillin (AMO) resulted in encouraging Helicobacter pylori cure rates in pilot and control studies. The aim of this study was to establish whether OME + AZI in combination with either AMO or ACA (amoxicillin plus clavulanic acid) are effective in curing H. pylori infection. A hundred patients with active duodenal ulcer and H. pylori infection were treated with OME (day 1-10: 2 x 40 mg/day, day 11-24: 40 mg/day, day 25-42: 20 mg/day) plus AZI 500 mg/day for the first 6 days. Patients were randomly assigned to either AMO 2 x 1000 mg/day (group A, n = 50) or ACA 2 x 1250 mg/day (group B, n = 50) during the first 10 days of treatment. H. pylori status was determined by urease test and histology before and 6 weeks after completion of therapy. Ninety-five patients completed the study. H. pylori infection was eradicated in 85.4% (41/48) patients from group A (intention-to-treat (ITT) analysis: 82%) versus 91.5% (43/47) patients from group B (ITT) analysis: 86%) (NS). All ulcer had healed after 42 days of omeprazole treatment. Side effects, usually minor, were recorded in 12.5% (group A) and 14.9% (group B) of patients (NS). Therapy had to be discontinued in two patients (one in group A and one group B) only. Ten-days treatment with OME and AZI (for the first 6 days) with AMO or ACA are simple and highly effective regimens to cure H. pylori infection in patients with duodenal ulcer disease.     

Evaluation of Haemophilus influenzae isolates with elevated MICs to amoxicillin/clavulanic acid

Electrophoretic and chromatographic experiments performed under straightforward conditions do not always provide satisfactory resolution. An obvious approach, then, is to manipulate the magnitude of relevant separation parameters, such as charge (zeta potential), size, and hydrophobicity, all of which can be accomplished by complex formation. This alternative has been studied with both a neutral, an anionic, and a cationic derivative of beta-cyclodextrin in an attempt to increase the resolution of peptides and proteins in free-zone electrophoresis utilizing the capillary format. The investigation showed that charged beta-cyclodextrins are suitable for this purpose. As expected, the effect seems to be most significant for substances with a small net surface charge, i.e., low mobility. Consequently, it may be advantageous to choose a pH of the buffer that is not far from the isoelectric point of the solutes. It should be emphasized that changes in the electropherograms observed upon addition of any complexing agent to the buffer may involve improvement or worsening of the resolution. Only by experimentation can one determine whether complexation with cyclodextrins favors resolution, since our knowledge about the interactions taking place is limited. However, if a positively (negatively) charged beta-cyclodextrin decreases the resolution of an acidic (basic) protein, one can expect theoretically, a negatively (positively) charged beta-cyclodextrin to increase the resolution, as was verified experimentally. The difference in mobility between two peaks caused by the complexation with cyclodextrins need not be larger than 2-3% for satisfactory resolution because the peaks are sharp. We have introduced a new definition for the resolution of two very adjacent peaks--the most common and interesting case in real-world analyses--that does not require measurement of peak widths.     

An unusual case of amoxicillin/clavulanic acid-related hepatotoxicity

Subcutaneous granuloma annulare (SGA) is little known to radiologists. Better knowledge of this lesion may prompt accurate diagnosis. A typical case is presented with plain radiography, ultrasound and MR imaging, and is confirmed by histology. When an otherwise healthy child presents with a rapidly growing, solitary, nontender, subcutaneous soft tissue mass, located on the scalp or extensor aspect of the limbs, that radiologically presents as an indistinct radiodense and hypoechoic mass, isointense to muscle on T1- and slightly hypointense to fat on T2-weighted MR images, without calcifications, bone involvement or extracompartmental invasion, SGA should be suspected.     

Multicentre comparative study of the efficacy and safety of azithromycin compared with amoxicillin/clavulanic acid in the treatment of paediatric patients with otitis media

An open multicentre study was conducted in 484 children between the ages of 6 months and 12 years with otitis media to compare the efficacy, the safety and the tolerance of once-daily azithromycin given for three days versus thrice-daily amoxicillin/clavulanic acid (CA) given for ten days. A satisfactory response (cure plus improvement) was noted 10 to 14 days after the start of treatment in 199 of 215 (92.6%) azithromycin-treated children and in 186 of 198 (93.9%) amoxicillin/CA-treated children. The relationship between treatment and clinical response was independent of chronicity of infection and the presence or absence of a perforated eardrum. Improvement in signs and symptoms of otitis media occurred significantly more rapidly in the children treated with azithromycin. Treatment-related or possibly treatment-related adverse events were recorded in 11 of 243 (4.5%) azithromycin-treated patients and in 20 of 240 (8.3%) treated with amoxicillin/CA. No patients in the azithromycin treatment group were withdrawn from treatment, but six amoxicillin/CA patients, including two < 2 years of age, discontinued treatment prematurely because of adverse events; the difference between treatment groups was statistically significant (p = 0.0146). It is concluded that azithromycin given as an oral suspension once daily for three days is as safe and effective as amoxicillin/CA given thrice daily for ten days in the treatment of children with otitis media.     

Amoxicillin and clavulanic acid concentrations in gingival crevicular fluid

The beta-lactams are bactericidal antibiotics, but some of them may be inactivated by bacterial beta-lactamases which destroy the beta-lactam ring. The inactivation of amoxicillin by beta-lactamases of gram negative anaerobic bacteria can be circumvented by the addition of clavulanic acid, a beta-lactamases inhibitor. Thus, most of these bacteria are susceptible to this combination. The aim of this study was to investigate the concentrations of amoxicillin and clavulanic acid in gingival crevicular fluid (GCF). These concentrations were measured in 20 patients with rapidly progressive periodontitis 1 h after a dose of 500 mg (1 tablet Augmentin) on day 0 and 1 h after the 10th intake on day 3. For the sampling of GCF, Periopapers were introduced in 16 gingival sites per subject and time. The GCF volumes collected were estimated using the Periotron 6000. A high performance liquid chromatography method has been developed for the determination of amoxicillin and clavulanic acid in microsamples (1 to 10 microliters) of GCF. The concentrations of amoxicillin and clavulanic acid were respectively, 14.05 micrograms ml-1 and 0.40 microgram ml-1 at day 0, 13.93 micrograms ml-1 and 0.37 microgram ml-1 at day 3. Effective levels of amoxicillin and clavulanic acid, well above the minimal inhibitory concentrations of some susceptible periodontal anaerobes (P. intermedia) involved in destructive periodontal diseases, are achieved following the multiple administration of amoxicillin combined with clavulanic acid.     

The role of clinical pharmacology in molecular genetics

PROBLEM: Discovering the causes of unusual phenotypes in human subjects is an important aspect of patient-oriented research. MATERIAL: The tools of clinical pharmacology are uniquely useful in addressing these problems. PATIENTS, SUBJECTS, OR CASE HISTORIES: We evaluated a 42-year-old patient with lifelong orthostatic hypotension and ptosis of the eyelids. He underwent a series of biochemical, physiological, and pharmacological tests outlined in this article. RESULTS: These studies indicated that sympathetic innervation was intact but that the sympathetic neurotransmitter was dopamine rather than norepinephrine. These results demonstrated that dopamine-beta-hydroxylase deficiency underlies the clinical abnormalities of this patient. CONCLUSION: In selected individuals with unusual phenotypes, the techniques of clinical chemistry and clinical pharmacology can define the nature of the defect at almost the resolution of the human genome.     

The taxoids. Comparative clinical pharmacology and therapeutic potential

Paclitaxel and docetaxel are 2 compounds from the new taxoid class of anti-cancer agents. Both drugs are very similar in preclinical activity, mechanism of action and spectrum of clinical activity. Some subtle differences in the intracellular retention of docetaxel may account for its lack of schedule-related myelosuppression and greater potency, and may be relevant to the skin toxicity and oedema which it produces. Early data suggest that there may be differing behaviour of anthracycline/taxoid combinations with respect to cardiotoxicity. Paclitaxel has been studied in several first-line combination therapy trials in ovarian cancer. Here, paclitaxel in combination with a platinum compound seems to have proven itself as a standard regimen. It is uncertain if docetaxel will be evaluated in this context. An abundance of clinical data is available for both analogues in the advanced, metastatic setting of breast cancer. Both also have been compared as single agents with doxorubicin with the results suggesting paclitaxel in a 3-hour infusion is inferior to the anthracycline (in terms of response rate), and those of docetaxel suggesting it is superior to the same dose of doxorubicin. This indirect comparison favours the activity of docetaxel; however, it is clear that in the dose/schedules studied, the taxoid compounds are not equitoxic. Either agent by itself, in the treatment of metastatic breast cancer, remains appropriate; however, lack of cumulative toxicity may make paclitaxel more attractive in some situations where prolonged administration is foreseen. Lung cancer trials have also confirmed the activity of both agents, although docetaxel appears to have slightly more promising activity in previously treated patients than paclitaxel. Paclitaxel in combination with cisplatin has been evaluated in randomised trials as first-line treatment of non-small-cell lung cancer (NSCLC). The results of these trials taken together suggest that this combination has an impact on survival similar to other new regimens now considered 'standard' in the front-line setting in this disease. Unfortunately, despite all the phase II data generated in numerous tumour types, little else can be said about the role of either taxoid in the 'standard' management of malignant disease. It will be some years yet before taxoid-based combinations have been evaluated sufficiently in randomised trials such that the impact of this novel class can be adequately assessed in terms of survival and cure rates.     

The problems of the experimental and clinical pharmacology of venotropic drugs

The article deals with problems of phenomenology of the selective vasomotor response of veins to the effect of drugs, analyses the peripheral and central hemodynamic effects of venotropic drugs, discusses and systematizes the principles of correct quantitative evaluation of venomotor reactions. Some representatives of the group of venotropic drugs are characterized and the main problems of their clinical use are discussed. The problems of promising trends of research are formulated.     

Professional and social responsibilities of clinical pharmacology

According to the decision of the Scientific and educational board of the Medical Faculty in Novi Sad the Institute for pharmacology toxicology and clinical pharmacology introduced the clinical pharmacology in 1975. Postgraduate studies were organized for those wishing to specialize, i.e. to get their M.Sc. degree in clinical pharmacology. Besides the youngest members of the Institute (now they are all associate professors) these studies were successfully completed by many doctors from other clinics or those employed in pharmaceutical industry. The publications which the Institute published from the field of pediatric clinical pharmacology were the very first ones not only in our country but also in world proportions. International methods for the evaluation (DDD, ATC code) of the scope and structure of drugs usage were introduced and modified according to our conditions and requirements. The studies on the usage of drugs were among the first pharmacoepidemiological studies in country and abroad. On the basis of these activities the Institute was two times the organizer of the scientific meeting sponsored by WHO. As a response to a sudden increase of the need for information on drugs due to disturbed supply and distribution of drugs from abroad (through humanitarian aid) a telephone and modem information service has been organized within the Institute. The printing of the book titled Drugs in Use was initiated (five editions since 1992) together with the issues on computer discs. The publishing of the journal Pharmaca Iugoslavica was also started under the auspices of the Association of Health Care Organizations. The service for adverse events registration was also organized. Through its activities in planning and organization of pharmacokinetic and clinical investigations, development of new analytic methods and performance of pharmacokinetic studies the Institute contributed to the development of new drugs and gave new theoretical solutions in pharmacokinetics. The Institute also initiated the establishment of the Committee for drugs of the Medical Faculty. Its professors are members of the Commission for Social Insurance, Federal Commission for Drugs and Federal Commission for Poisons. Through all mentioned activities the Institute has greatly influenced not only our but also general medical community.     

Methodology of kinetic interaction studies in clinical pharmacology: an experimental contribution on diftalone and acetylsalicylic acid

The possible interaction of acetylsalicylic acid (ASA) and diftalone (DIF), a new anti-inflammatory drug, was studied in 6 volunteers. All subjects received each of the following three treatments: ASA 1 g, DIF 0.5 g, ASA 1 g plus DIF 0.5 g at 4-day intervals (stage 1 of the study). In stage II of the same study, each subject received ASA 1 g plus DIF 0.5 g in three different occasions 1 week apart; after a 7-day pre-treatment with either DIF 0.25 g b.i.d., or ASA 0.5 g b.i.d., or DIF 0.25 g b.i.d. plus ASA 0.5 g b.i.d. A total of four different comparisons were made. After pre-treatment with DIF, but not after pre-treatment with DIF plus ASA, the peak level of salicylate was significantly reduced by about 15%. No other evidence of interaction was found.     

Initial experience of clinical pharmacology and clinical pharmacy interactions in a clinical pharmacokinetics consultation service

International statistics indicate that there is a close correlation between the consumption of saturated fats (dairy fats and meat fats) and the mortality from coronary heart disease (CHD), and this conception has been confirmed by many epidemiological studies. Such studies alone, however, cannot prove the existence of a cause-and-effect relationship between these two variables; dietary intervention trials are needed. The Finnish Mental Hospital Study was such a trial, conducted in two hospitals near Helsinki in 1959--1971. Practically total replacement of dairy fats by vegetable oils in the diets of these hospitals was followed by a substantial reduction in the mortality of men from CHD. Total mortality also appeared to be reduced. As to the causes of death other than CHD, none was significantly influenced by dietary change. This was also true for malignant neoplasms. To alleviate the burden of CHD on public health, many investigators have recommended important changes in the quantity and quality of dietary fats.     

Departments of clinical pharmacology and therapeutics as sources of data

The functions of a clinical pharmacologist are described and some questions worth asking when prescribing drugs are listed and briefly discussed.     

A reassessment of ticarcillin/clavulanic acid dose recommendations for infants, children and adults

Breast reconstruction is frequently performed for and requested by women with breast cancer. There are continued concerns about the safety of this procedure. We reviewed the Medical College of Georgia experience with immediate breast reconstruction to determine overall morbidity and whether premorbid risk factors could predict complications. Patients were reviewed with attention to epidemiologic characteristics, comorbid medical conditions, and risk factors; hospital and operative course; immediate wound complications; and patient survival. t test and chi-square analysis were performed to determine risk factors for developing wound complications. Between October 1990 and December 1996, 55 patients underwent 62 mastectomies and immediate reconstruction for breast cancer or contralateral prophylaxis. There were 13 stage 0, 23 stage I, 16 stage II, 4 stage III, and 1 stage IV tumors. There were 19 prosthetic and 43 autologous tissue reconstructions. Eighteen patients had 24 wound complications. Major complications occurred in eight patients and required reoperation for implant removal (two bilateral), ventral herniorrhaphy, and split thickness skin grafting for tissue loss. Patients who were obese were statistically more likely to develop surgical wound complications. Tobacco use, age, comorbid medical illness, operative blood loss, length of operation, and length of hospital stay did not predict for the development of wound complications. Patients who underwent prosthetic reconstruction had a significantly higher rate of major wound complications when compared with those who had autologous reconstruction. There was a single case of delay of chemotherapy secondary to surgical wound complication. There were no cases of autologous flap loss or local recurrence. Median survival is 23 months (1-72 months). At last follow-up, 53 patients are alive and without evidence of local recurrence. Breast reconstruction may be performed safely for most breast cancer patients. Autologous tissue reconstruction is preferred and carries significantly less major morbidity. Reconstruction should not delay adjuvant chemotherapy.     

Development, pharmacology and clinical experience with clomiphene citrate

This review describes the development and pharmacology of clomiphene and those specific characteristics of both drug and patients which determine its clinical efficacy. The studies reviewed describe clinical observation of patient characteristics (age, additional infertility diagnosis, semen quality), vaginal ultrasound observations of ovaries (number and size of pre-ovulatory follicles) and endometrial lining (thickness, pattern) in 2841 clomiphene cycles in patients who required intrauterine insemination (IUI) because of poor sperm quality or an unsatisfactory postcoital test. They show that (i) conception in clomiphene cycles is related to the number and size of pre-ovulatory follicles, endometrial thickness, patient age, pelvic adhesions, type of anovulatory disorder and semen quality; (ii) pregnancy rates per clomiphene-IUI cycle are constant through at least six cycles; (iii) multiple births cannot be prevented by withholding human chorionic gonadotrophin or advising against coitus when multiple pre-ovulation follicles are present unless all follicles down to 10-12 mm diameter are counted. We also reviewed pregnancy outcome (number of gestational sacs, babies, preclinical and clinical abortion, ectopic pregnancy and birth sex) in 1744 clomiphene pregnancies from our clinic. We found that (i) preclinical and clinical abortions are increased only slightly by clomiphene use, compared to spontaneous pregnancy; (ii) clinical abortions are decreased in patients with polycystic ovaries and luteal insufficiency who use clomiphene; (iii) conception and preclinical abortions are related to endometrial thickness prior to ovulation; (iv) ectopic pregnancies are not increased by clomiphene and (v) the ratio of male births is not altered by clomiphene, except possibly in timed insemination cycles. These studies repudiate many misconceptions regarding clomiphene. They also show that clinical outcome may be improved by pre-ovulation ultrasound monitoring of ovarian and endometrial response.