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Background: There is concern about an increasing infiltration of markets by substandard and fake medications against life-threatening diseases in developing countries. This is particularly worrying with regard to the increasing resistance development of Plasmodium falciparum against affordable anti-malarial medications, which has led to a change to more expensive drugs in most endemic countries., Methods: A representative sample of modern anti-malarial medications from licensed (public and private pharmacies, community health workers) and illicit (market and street vendors, shops) sources has been collected in the Nouna Health District in north-western Burkina Faso in 2006. All drugs were tested for their quality with the standard procedures of the German Pharma Health Fund-Minilab. Detected low standard drugs were re-tested with European Pharmacopoeia 2.9.1 standards for disintegration and ultraviolet-visible spectroscopy at the laboratory of the Heidelberg University for confirmation., Results: Overall, 86 anti-malarial drug samples were collected, of which 77 samples have been included in the final analysis. The sample consisted of 39/77 (50%) chloroquine, 10/77 (13%) pyrimethamine-sulphadoxine, 9/77 (12%) quinine, 6/77 (8%) amodiaquine, 9/77 (12%) artesunate, and 4/77 (5%) artemether-lumefantrine. 32/77 (42%) drug samples were found to be of poor quality, of which 28 samples failed the visual inspection, nine samples had substandard concentrations of the active ingredient, four samples showed poor disintegration, and one sample contained non of the stated active ingredient. The licensed and the illicit market contributed 5/47 (10.6%) and 27/30 (90.0%) samples of substandard drugs respectively., Conclusion: These findings provide further evidence for the wide-spread existence of substandard anti-malarial medications in Africa and call for strengthening of the regulatory and quality control capacity of affected countries, particularly in view of the now wider available and substantially more costly artemisinin-based combination therapies.

In this paper, three different HPLC methods for the quantification of thalidomide in tablets were developed and compared. The comparison of a conventional method at 30 degrees C with two high-temperature methods at 180 degrees C showed equal results. Using high-temperature HPLC (HT-HPLC), faster analysis times could be achieved. We have also focused on analyte stability and could show that the stationary phase has a pronounced effect on the on-column degradation of thalidomide at high temperatures. Virtually no degradation occurs if a polystyrene divinylbenzene column is used, whereas thalidomide is completely degraded at 180 degrees C when a carbon clad zirconium dioxide column is used.

Introduction: Changes in drug treatment are frequently mandatory with hospital admission and discharge because hospital drug formularies are generally restricted to about 3000 drugs as compared to the many times this number - 62,000 in Germany - that are commercially available. Without computerised support, the process involved with switching drugs to a corresponding generic or a therapeutic equivalent is time-consuming and error-prone., Methods: We have developed and tested a standardised interchange algorithm for subsequent implementation into a computerised decision support system that switches drugs to the corresponding generic or a therapeutic equivalent if they are not listed on the hospital drug formulary., Results: The algorithm was retrospectively applied to the medication regimens of 120 patients (774 prescribed drugs containing 886 active ingredients) at their time of admission to surgical wards. Of the prescribed drugs, 52.8% (409/774) were part of the hospital drug formulary, thereby rendering a switch unnecessary. The 365 drugs not listed consisted of 392 active ingredients that were successfully switched to a corresponding generic (84.7%) or a therapeutic equivalent (10.2%). No specific switching procedures were defined for only 2.3% (20/886) of the active ingredients. In these cases, the drugs were either discontinued (4/20) or special drug classes, current diseases or co-medication required manual switching (8/20), or the drugs were continued unchanged and ordered from a wholesaler (8/20)., Conclusion: Using a standardised interchange algorithm, pre-admission drug regimens can successfully be switched to drugs on a hospital drug formulary. These findings suggest that a computerised decision support system will likely be useful to support this important practice.

Background: Posaconazole is a new broad-spectrum triazole antifungal drug that is used in prophylaxis and therapy of opportunistic fungal infections in immunocompromised patients. Up to now, it is available as an oral suspension only. Due to variable systemic availability known from other azoles, such as itraconazole, it is important to measure blood levels, especially in patients undergoing abdominal surgery which may influence the intestinal resorption., Methods: A sensitive and selective high-performance liquid chromatography method for the precise determination of posaconazole and the internal standard clotrimazole in human plasma was developed and validated. Samples were extracted using solid-phase extraction and separated on a reversed-phase C8 column (150 x 4.6 mm, 5 microm) using phosphate buffer (pH 6.7, 0.04 M):acetonitrile:methanol (43:49:8, v/v/v) as mobile phase. UV detection was performed at 260 nm., Results: This method showed that a lower limit of quantification was 50 ng/mL and the limit of detection 3 ng/mL. Linearity was tested in the range from 50 to 5000 ng/mL (r(2)=0.9998). Mean recovery was 86%., Conclusions: The method proved to be a useful tool for therapeutic drug monitoring. It is specific, precise and showed excellent reproducibility as well as a favourable accuracy.

Background: Linezolid is an important therapeutic option for the treatment of infections caused by multiresistant Gram-positive bacteria such as vancomycin-resistant Enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). However, the clinical benefit of linezolid is threatened by the emergence of resistant strains of MRSA and VRE reported in North America and Europe. For effective antimicrobial treatment, it is extremely important to have exact knowledge of drug concentrations at the site of action., Methods: A simple HPLC method for the rapid and precise determination of linezolid in different biomatrices (e.g., plasma, soft tissue, bone, dialysis fluid and used microbiological broth) was developed and validated. Proteins were precipitated with acetonitrile and separation was performed on a reversed-phase C8 column with a mobile phase consisting of water/acetonitrile (80:20, v/v). UV detection was performed at 251 nm., Results: This method has a lower limit of quantification of 0.3 microg/mL and a linear calibration range of 0.5-40 microg/mL. The method showed excellent reproducibility, with an inter- and intra-day assay precision of <5% (% relative standard deviation), as well as excellent accuracy, with inter- and intra-day assay accuracy ranging from 100.6% to 103.2%. Stability up to 6 months in water and plasma was proven. Quantitative recovery was possible after up to three freeze thaw cycles., Conclusions: The method is useful in the acquisition of in vivo and in vitro data. It is simple, flexible, specific, precise and reproducible, as well as of adequate sensitivity for clinical use.

From all topical otic preparations, eardrops are the most often used drug-containing application forms. There are some advantages for those ototopical drops like achievement of high concentration, good compliance, and rapid delivery. Furthermore those drugs are easy to administer. The risk of adverse drug reactions due to eardrops is small.

The treatment of eye diseases requires particular galenic preparations, because the eye is a sensitive organ. The preparation has to be sterile and should not irritate in a physical or chemical way. Ideally the physiological condition of the eye should be mimicked in the development of a preparation. The application form influences the intensity and duration of the therapeutic effect. Many people are affected by the so-called office-eye-syndrome. The treatment is both non-medical and medical for example with artificial teardrops. The preparation should be chosen according to the severity of the disease and the viscosity of the preparation.

Interactions between immunosuppressants and antiinfectives are most important in pharmacotherapy. Patients receiving this drug combination must be monitored carefully. Individual dose adaptation and therapeutic drug monitoring (TDM) according to the SOAP scheme (subjective data, objective data, analysis, plan) are exemplified by the case report of a 47-year-old patient who had undergone a liver transplantation.

Objectives: Linezolid is an oxazolidinone antibiotic used in the treatment of infections caused by vancomycin-resistant enterococci. Resistance to linezolid has been associated with a G2576U mutation in domain V of the 23S rRNA., Patient and Methods: We present clinical details and susceptibility data from multiple Enterococcus faecium strains isolated from a liver transplant patient over 13 months. MICs of linezolid, vancomycin and quinupristin/dalfopristin were determined using Etest. Molecular typing was performed by pulsed-field gel electrophoresis. Domain V of the 23S rRNA gene in the vancomycin-resistant Enterococcus faecium was amplified. Linezolid concentrations were analysed by HPLC., Results: We report the emergence of resistance to linezolid in a vancomycin-resistant Enterococcus faecium during linezolid treatment. After discontinuation of the linezolid therapy, the isolate reverted to susceptibility. However, after re-administration of linezolid the vancomycin-resistant Enterococcus faecium became resistant to linezolid again. The isolates that were resistant to linezolid had a G2576T mutation in their 23S rDNA., Conclusion: We describe a clinical case that shows the shift of a vancomycin-resistant Enterococcus faecium from linezolid resistance to susceptibility and then back to resistance again related to linezolid therapy.

Menkes' Kinky Hair Syndrom is a rare, X-linked recessive multisystemic lethal disorder of copper metabolism. Male infants who are affected usually die at the age of 2-3 years. If the disease is diagnosed early, patients profit from subcutaneously administered copper salts. We describe the preparation and stability of a copper-histidin solution. This solution has some advantages in terms of stability over the solutions described in earlier publications. This is a great advantage for the patients and their parents, because an ambulatory care or a home care of this patients is possible now.

Stability of voriconazole in infusion bags The dosage of i.v. administered voriconazole in adults and children is body weight based. For this reason an individual preparation is necessary in those patients. Further stability data were needed for a central production in the hospital pharmacy department, however. Three concentrates and three bags were produced (day 1) according to the procedures given by the product leaflet. Our data shows that the ready to use bag and the concentrate solution is stable at 2-8 degrees C for 32 days.

Objective: The combination of chloroquine and methylene blue is potentially effective for the treatment of chloroquine-resistant malaria caused by Plasmodium falciparum. The aim of this study was to investigate whether methylene blue influences the pharmacokinetics of chloroquine., Methods: In a randomized, placebo-controlled, parallel group design, a 3-day course of therapeutic oral doses of chloroquine (total 2.5 g in male, 1.875 g in female participants) with oral co-administration of placebo or 130 mg methylene blue twice daily for 3 days was administered to 24 healthy individuals. Chloroquine, desethylchloroquine, and methylene blue concentrations were determined by means of HPLC/UV or LC/MS/MS assays in whole blood, plasma, and urine for 28 days after the last dose., Results: During methylene blue exposure, the area under the chloroquine whole blood concentration-time curve normalized to body weight (AUC(0-24 h)/BW) yielded a trend of reduction (249+/-98.2 h mug l(-1) kg(-1) versus 315+/-65.0 h mug l(-1) kg(-1), P=0.06). The AUC(0-24 h)/BW of desethylchloroquine was reduced by 35% (104+/-40.3 h mug l(-1) kg(-1) versus 159+/-66.6 h mug l(-1) kg(-1), P=0.03), whereas the metabolic ratio between chloroquine and desethylchloroquine remained unchanged (2.25+/-0.49 versus 1.95+/-0.42, P=0.17). The renal clearance of chloroquine and the ratio between chloroquine in whole blood and plasma remained unchanged (P>0.1)., Conclusion: Oral co-administration of methylene blue appears to result in a small reduction of chloroquine exposure which is not expected to be clinically relevant and thus represents no concern for further development as an anti-malarial combination.

Objective: Moxifloxacin is a recently developed fourth-generation methoxyquinolone with a broad spectrum of activity against both Gram-positive and Gram-negative aerobic bacteria and anaerobes. The aim of the present study was to assess the penetration of moxifloxacin into gastrointestinal (GI) mucosal tissues to evaluate its potential role as an antimicrobial drug in bacterial infections of the GI tract., Patients and Methods: Twenty-eight patients undergoing GI-tract surgery received 400 mg of moxifloxacin twice pre-operatively [eight patients orally (po) and 20 patients intravenously (iv)], of whom 22 completed the study. Mucosal tissues (three stomach, three small bowel and 16 colon) and serum samples were collected and moxifloxacin concentrations were measured by HPLC., Results: The highest tissue concentrations were detected in the mucosa of the stomach (10.9 +/- 5.1 mg/kg), followed by colon mucosa (7.8 +/- 7.1 mg/kg after iv; 6.6 +/- 3.6 mg/kg after po) and small bowel mucosa (5.4 +/- 0.5 mg/kg). The tissue-to-serum ratio of moxifloxacin was 2.0 +/- 1.6 in the small bowel mucosa, 5.8 +/- 3.4 and 6.8 +/- 3.9 in the colon mucosa after po and iv administration, respectively, and 9.7 +/- 5.7 in the stomach mucosa., Conclusion: Moxifloxacin penetrates into and accumulates in the mucosa of the stomach, small bowel and colon. The clinical applicability of moxifloxacin administration for bacterial GI-tract infections should be investigated in controlled trials.

Background: The pharmacokinetics of digoxin is modulated by the efflux pump P-glycoprotein. Cremophor EL (BASF Aktiengesellschaft, Ludwigshafen, Germany) (polyoxyl 35 castor oil), a castor oil derivative used to improve the solubilization of drugs and vitamins, has been shown to inhibit this membrane transporter in vitro and in vivo. So far, no study in humans has evaluated the effect of Cremophor RH40 (BASF Aktiengesellschaft) (polyoxyl 40 hydrogenated castor oil) on P-glycoprotein., Methods: A randomized, double-blind, placebo-controlled crossover study in 12 healthy individuals was performed with a single oral dose of 0.5 mg digoxin in a hard gelatin capsule in combination with multiple doses of oral Cremophor RH40 (600 mg 3 times daily) or placebo. A digitized electrocardiogram with 12 standard leads was recorded to assess the pharmacodynamics of digoxin., Results: Cremophor RH40 delayed and enhanced the absorption of digoxin in the first 5 hours after dosing. During Cremophor RH40 administration, digoxin lag time was significantly prolonged compared with placebo (0.53 +/- 0.25 hour versus 0.36 +/- 0.19 hour, P =.04). The peak concentration of digoxin increased by 22%, from 2.21 +/- 0.94 ng/mL to 2.69 +/- 1.28 ng/mL (P =.06). Similarly, the area under the plasma concentration-time curve from 0 to 5 hours significantly increased by 22% (5.23 +/- 1.63 h. ng/mL versus 4.30 +/- 1.12 h. ng/mL, P =.03). Digoxin did not cause a clinically significant change in the dynamic parameters during both periods., Conclusion: This study demonstrates a pharmacokinetic and pharmaceutic interaction between the emulgent Cremophor RH40 and digoxin, caused by P-glycoprotein inhibition and prolongation of the dissolution time of digoxin tablets by Cremophor RH40, respectively. Our in vivo study in humans supports the validity of in vitro observations on P-glycoprotein.

As potential modulators of drug safety and effectiveness the compatibility and stability of drugs are important elements in drug prescription and drug administration to patients. According to various characteristics, important differences between areas of stationary hospital care and ambulatory care are evident. While the challenges in the ambulatory care setting have been focussed on dermatological topical medication, incompatibility assessment is a challenge for the physician and the pharmacist in a hospital setting. Particularly in intensive care patients often up to 20 different drugs are administered in only few infusion devices or through a limited number of parenteral infusion lines. Among the compounds most often incriminated to cause incompatibilities are furosemide, phenytoin, midazolam and diazepam when used as i.v. admixtures. In recent years new challenges arose in ambulatory care in the area of oncologic treatment. Cytotoxic drug therapy and supportive care therefore requires increasing attention in terms of incompatibility of ready to use combined drug admixtures. To prevent incompatibilities never more than one drug should be added, nutrition solutions should never be used as carrier solutions for drug administration, mixtures should not be stored and should be administered immediately after preparation. During the administration of unavoidable mixtures visible changes of the solutions should be carefully sought.