European Journal of Clinical Pharmacology

A survey among hospital staff physicians was conducted in order to evaluate their attitudes towards systemic antimicrobial agents. Direct questions about the value of different agents and choice within pairs of antimicrobial drugs, stating the reasons for the preference, were included in the questionnaire used. Gentamicin, penicillin G and ampicillin were the most popular antibiotics among respondents. On the other hand, ampicillin, penicillin G, sulfonamides, tetracycline and aminoglycosides were the agents perceived as most often associated with side-effects. Low toxicity, bactericidal effect, diffusion in the body and familiarity with the drug were acknowledged as the most important attributes in choice of a systemic antimicrobial agent, but a broad spectrum of antibacterial activity appeared as a major determinant in the choice of these drugs when physicians were asked to select one substance from members of several pairs listed. The results suggest that certain important misconceptions may have played a substantial role in the prescribing habits of the physicians surveyed.

Relaxation of the renal pelvic smooth muscle is usually attempted as a symptomatic treatment in painful colic of the upper urinary tract. The spasmolytic potency of morphine, pethidine, pentazocine, fentanyl, naloxone and papaverine was evaluated using noradrenaline-contracted pelvic strips from hydronephrotic patients. The order of spasmolytic potency was found to be fentanyl > pethidine = papaverine > pentazocine = naloxone. Morphine produced a dual effect, starting with contraction followed by relaxation. Norpethidine, which is the only metabolite of pethidine occurring in human plasma, had the same relaxing potency as its parent compound, pethidine. Thus, an active metabolite may play a role in the outcome of spasmolytic drug treatment.

Objective: The Effect of omeprazole, a proton pump inhibitor, and cimetidine, an H2-receptor antagonist, on plasma aldosterone (PA) response to angiotensin II (AII) were evaluated. Methods: Furosemide (a loop diuretic agent, 20 mg) was given intravenously to eight healthy subjects during a control period, and after pretreatment with omeprazole (20 mg daily) or cimetidine (800 mg daily) for 6 days. Blood samples for determination of plasma renin activity (PRA), AII, PA, adrenotorticotropic hormone (ACTH) and potassium were obtained just before, and 30, 60 min and 120 min after furosemide administration. Results: PRA, AII and PA increased significantly after furosemide administration whereas ACTH and potassium did not. Significant correlations between plasma AII and PA were obtained in the control and omeprazole trial, but not in the cimetidine trial. The slope of the regression lines of the control and omeprazole trials did not differ significantly. Conclusion: These results suggest that, in contrast to cimetidine, the inhibitory effect of omeprazole on AII-stimulated aldosterone production following dosing with furosemide is negligible.

After screening a local population in the northern part of The Netherlands for hypertension, 59 patients with a diastolic pressure (DP) between 95 and 130 mmHg were randomized and treated either with 50 mg atenolol (n=29) or 100 mg atenolol (n=30) for 1 month. There was no significant difference between the two treatments, neither in the fall in systolic and diastolic pressures nor in the number of complaints reported. It is concluded that in the initial treatment of uncomplicated mild to moderate hypertension, 100 mg atenolol has no advantage over a 50 mg dose.

Cancer chemotherapy was introduced at the same time as antibacterial chemotherapy but has not been nearly such a success. However, there is a growing optimism in oncology today due to the introduction of several more or less target-specific drugs as complements to the conventional cytotoxic drugs introduced half a century ago. The success in the treatment of chronic myelogenous leukemia by imatinib, inhibiting the bcr-abl-activated tyrosine kinase and thereby interrupting the signal transduction pathways that lead to leukemic transformation with impressive survival benefit, has paved the way for this new optimism. Another success story is the introduction of trastuzumab in breast cancers overexpressing the HER-2 receptor. In contrast, there has been little progress in other malignancies such as metastatic malignant melanoma, although very recently, clinical trials with new targeted drugs have shown increased survival. All major pharmaceutical companies now have ambitious development programs in the cancer area. However, the high costs of the novel drugs cause economic distress in the health care system in many countries leading to an intense debate on the cost-effectiveness of these drugs in relation to other health care activities.

In a pharmacokinetic study of the new analgesic and anti-inflammatory drug indoprofen, plasma levels and urinary excretion were determined in four healthy volunteers after 100 mg and 200 mg iv, and after 100 mg (capsules) and 200 mg (tablets) oral doses. After iv administration, the mean biological half-life (t1/2 β) was about 2 h (range 1.4 to 3.2 h). The apparent volume of distribution Vdβ ranged between 11 to 17 % of body weight, indicating its limited extravascular distribution. Most of the drug was excreted in urine as glucuronide and a smaller proportion as unchanged indoprofen: the 24 h urinary excretion of these compounds accounted for 67 to 95 % of an iv dose. Peak plasma levels occurred between 30 and 120 minutes after oral administration of 100 mg as capsules or 200 mg as tablets. The mean biological half-life was about 2 h, as after iv administration. The bioavailability of oral doses was assessed using both plasma levels and urinary excretion data. The absorption of capsules and tablets was practically complete, that of the former being faster.

This study aimed to test the applicability and effectiveness of the principles and informed consent form (ICF) template proposed by the Strategic Initiative for Developing Capacity in Ethical Review (SIDCER) across multiple clinical trials involving Thai research participants with various conditions. A single-center, randomized-controlled study nested with eight clinical trials was conducted at Thammasat University Hospital, Thailand. A total of 258 participants from any of the eight clinical trials were enrolled and randomly assigned to read either the SIDCER ICF (n = 130) or the conventional ICF (n = 128) of the respective trial. Their understanding of necessary information was assessed using the post-test questionnaire; they were allowed to consult a given ICF while completing the questionnaire. The primary endpoint was the proportion of the participants who had the post-test score of ≥80%, and the secondary endpoint was the total score of the post-test. The proportion of the participants in the SIDCER ICF group who achieved the primary endpoint was significantly higher than that of the conventional ICF group (60.8 vs. 41.4%, p = 0.002). The total score of the post-test was also significantly higher among the participants who read the SIDCER ICF than those who read the conventional ICF (83.3 vs. 76.0%, p < 0.001). The present study demonstrated that the SIDCER ICF was applicable and effective to improve Thai research participants’ understanding of research information in diverse clinical trials. Using the SIDCER ICF methodology, clinical researchers can improve the quality of ICFs for their trials.

The aim of laboratory screening in Phase I is to exclude subjects with subclinical illness, who might be at increased risk in the study, and who might also adversely influence interpretation of the results. A new method for laboratory screening, based on Bayesian probability theory, is proposed, which consists of: Use of this deductive method in screening volunteers for Phase I trials affords increased security of selection, while reducing the number of non-pertinent exclusions because of laboratory findings.