First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound AIC246.

We report the first case of cytomegalovirus (CMV) disease treated with AIC246, a novel anti-CMV compound which targets the viral terminase complex and remains active against virus resistant to DNA polymerase inhibitors. A lung transplant recipient developed refractory multidrug-resistant CMV disease involving the lungs, gastrointestinal tract and retina. His disease progressed despite treatment with all DNA polymerase inhibitors; multiple agents reported to have activity against CMV in case series, and reduction in his immunosuppressive medications. AIC246 which is in clinical development was obtained for emergency use, and combined with additional reduction in immunosuppression resulted in rapid clinical, virological and radiological resolution of disease. The patient has remained free of CMV disease or viremia off treatment for greater than 3 months. In summary AIC246, while still in development, may be a promising alternative to current therapies.

High variation of tioguanine absorption in patients with chronic active Crohn's disease.

BACKGROUND: Tioguanine (thioguanine) has been suggested as a therapeutic alternative for patients with Crohn's disease resistant or intolerant to azathioprine or mercaptopurine. However, pharmacokinetic data on tioguanine in inflammatory bowel disease are missing. AIM: To determine the disposition of three different 40 mg tablet preparations of tioguanine in patients with Crohn's disease. METHODS: Six patients with chronic active Crohn's disease were included in a randomized, cross-over, single-dose study. Pharmacokinetic analysis was based on plasma concentrations of tioguanine during 6 h after dosing. Tioguanine was measured by a validated high-pressure liquid chromatographic method. RESULTS: The areas under the curve (AUC) varied 4-7-fold between patients. In two patients, tioguanine was not detected in plasma following the intake of one of the three tablets; another patient did not absorb tioguanine in two of the three different preparations. No significant differences were found in the AUC and Cmax values between the three tablets. In all patients, there was a second peak in plasma concentration following a meal 3 h after drug administration. CONCLUSIONS: The absorption of tioguanine is highly variable in patients with Crohn's disease, which may be responsible for treatment failure. Therapy with tioguanine may be improved by monitoring tioguanine nucleotides as a surrogate parameter of efficacy.

Adolescents' drug use and drug knowledge.

UNLABELLED: Self-medication is a common event. To use drugs correctly, a basic knowledge about drugs is required. Poor data are available about adults' drug knowledge. Furthermore, adolescents' basic drug knowledge has not been investigated. This study was designed in order to explore adolescents' drug use and knowledge and the factors that influence them. A total of 56 tenth grade students between 15-17 years of age at a secondary school in Dresden, Germany were enrolled in a pilot study by answering a self-completion questionnaire. Of adolescents, 57% took from one to six different drugs in the 2 weeks before questioning. In particular, a chronic consumption of non-opioid analgesics was found. Some 15% of adolescents took headache remedies at least several times per month. Self-acquisition occurred more often for these drugs than for any other drug group. The best score for drug knowledge was 10 out of 13 possible points and only 43% of students attained from 7 to 10 points. Astonishingly, more than two-thirds of adolescents could not describe in their own words how a medicinal agent is ingested. Female gender and a chronic drug consumption were detected as influencing factors of better drug knowledge. CONCLUSION: The results indicate that adolescents gain drug knowledge through drug consumption and not before taking drugs. This leads to a potential risk particularly in the case of self-medication.

Regional drug information service.

BACKGROUND: Drug information centers (DICs) were established in Europe more than two decades ago. The majority of German DICs were created in the 90s. The regional University hospital-based DIC, which offers services to physicans, is now in operation for three and a half years . OBJECTIVE: To evaluate the types of enquiries received and the profile of the users of a drug information service. METHODS: The working procedure at a regional center in Dresden, Germany, is described. The topics for consultation (adverse reactions, pharmacokinetics, etc.) are presented, and the types of drugs involved are classified according to the Anatomical Therapeutic Chemical (ATC) classification. Users are grouped by medical specialty. Future plans for the DIC are discussed. RESULTS: A total of 516 enquiries were received. Questions concerning therapeutic use (34%), adverse drug reactions (28%), pregnancy/lactation (16%), and pharmacokinetics/dosage (15%) were asked most frequently. Cardiovascular drugs (20%), systemic antiinfectives (19%) as well as drugs targeting the central nervous system (15%) and alimentation/metabolism (9%) were the predominant foci of enquiries. The major users of the DIC were internists (19%), general practitioners (19%), pediatricians (18%), and gynecologists (11%). CONCLUSIONS: The types of questions and users of this service were generally similar to those recorded at many other European DICs. The service has begun producing educational bulletins on drug-related topics of clinical relevance.