Dose adjustment of psychotropic drugs in patients with liver cirrhosis may be important as most of these drugs are predominantly eliminated by the liver and many of them are associated with dose-dependent adverse reactions. As no surrogate parameter is available to predict hepatic metabolism of drugs, dose adjustment according to pharmacokinetic properties of the drugs is proposed. Psychotropic drugs (antiepileptics, antiparkinsonian drugs, psycholeptics such as antipsychotics, anxiolytics, sedatives and hypnosedatives, and psychoanaleptics such as antidepressants, psychostimulants and antidementia drugs) marketed in Switzerland in 2006 were therefore classified according to their hepatic extraction and/or bioavailability to predict their kinetic behaviour in patients with cirrhosis. The expected changes in hepatic metabolism predicted by pharmacokinetic properties were compared with the results from kinetic studies carried out in patients with liver disease. These studies were identified using MEDLINE searches. Of the 116 psychotropic drugs available on the Swiss market by the year 2006, only 12 were predominantly eliminated through the kidney. For five substances, no Q(0) value (the dose fraction metabolized or excreted extra-renally) could be determined because of lack of pharmacokinetic data. Of 99 drugs with predominant hepatic metabolism, 29.3% were categorized as high, 25.2% as intermediate and 38.4% as low extraction drugs, while seven substances could not be classified. Pharmacokinetic studies in patients with liver disease were available for 55 of these 99 drugs eliminated predominantly by the liver (Q(0)-value > or = 0.5). Only a few kinetic studies in patients with liver disease were found for antipsychotics, antiparkinsonian drugs and antidepressants, except for selective serotonin reuptake inhibitors and some newer antidepressants. The expected changes in pharmacokinetics were generally in good agreement with the changes reported in pharmacokinetic studies. For 12 drugs, the observed changes in pharmacokinetics from clinical studies were different from the changes expected based on their classification. However, for low extraction drugs metabolized by cytochrome P450 isozymes, clearance may be reduced by up to 50%. In conclusion, the classification of drugs according to their hepatic extraction and/or bioavailability is a useful tool for dose adjustment, if information from clinical studies is lacking. There is a gap in information about pharmacokinetic changes in patients with liver cirrhosis for a large number of centrally acting drugs. Kinetic studies for centrally acting drugs with predominant hepatic metabolism should be carried out in patients with liver disease to allow precise dose recommendations for enhanced patient safety.

Dose adaptation for liver disease is important in patients treated with antineoplastic drugs because of the high prevalence of impaired liver function in this population and the dose-dependent, frequently serious adverse effects of these drugs. We classified the antineoplastic drugs marketed in Switzerland at the end of 2004 according to their bioavailability and/or hepatic extraction to predict their kinetic behaviour in patients with decreased liver function. This prediction was compared with kinetic studies carried out with these drugs in patients with liver disease. The studies were identified by a structured, computer-based literature search. Of the 69 drugs identified, 52 had a predominant extrarenal (in most cases hepatic) metabolism and/or excretion. For 49 drugs, hepatic extraction could be calculated and/or bioavailability data were available, allowing classification according to hepatic extraction. For 18 drugs, kinetic studies have been reported in patients with impaired liver function, with the findings generally resulting in quantitative recommendations for adaptation of the dosage. In particular, recommendations are precise for 16 drugs excreted by the bile (e.g. doxorubicin and derivatives and vinca alkaloids). Validation studies comparing such recommendations with kinetics and/or dynamics of antineoplastic drugs in patients with decreased liver function have not been published. We conclude that there are currently not enough data for safe use of cyctostatics in patients with liver disease. Pharmaceutical companies should be urged to provide kinetic data (especially hepatic extraction data) for the classification of such drugs and to conduct kinetic studies for drugs with primarily hepatic metabolism in patients with impaired liver function to allow quantitative advice to be given for dose adaptation.

Unter PID («pelvic inflammatory disease») und Entzündungen des oberen Genitaltrakts («upper genital tract infections») verstehen wir entzündliche Veränderungen des oberen weiblichen Genitaltrakts jeglicher Kombination: Endometritis, Salpingitis, Tuboovarialabszess, Peritonitis im kleinen Becken. Die International Infectious Disease Society for Obstetrics and Gynecology empfiehlt eine Revision der CDC-Richtlinien mit Berücksichtigung des Erregers bzw. des verursachenden Agens und des Schweregrades der Erkrankung. Infektionen mit Chlamydia trachomatis und Neisseria gonorrhoeae sind weltweit am Zunehmen und gelten als eine der Hauptursachen von tubarer Sterilität, chronischen Unterbauchschmerzen und ektopen Schwangerschaften. Über 30% der Infektionen verlaufen subklinisch oder asymptomatisch. Deshalb sollte bei jungen, sexuell aktiven Frauen mit Risiken ein generelles Screening durchgeführt werden. Die antibiotische Therapie sollte möglichst früh, im Zweifelsfall probatorisch, begonnen werden und ein breites Keimspektrum abdecken. C. trachomatis und Gonokokken werden spezifisch und resistenzgerecht therapiert. Bei leichten Verläufen scheint die ambulante Therapie keine Nachteile gegenüber einer Hospitalisation zu haben.