Effects of verapamil on the pharmacokinetics and metabolism of epirubicin

Summary Experimental data suggest that multidrug resistance in cancer may be overcome by using an increased dose of anticancer agent(s) in combination with a resistance-modifying agent (RMA). We studied the pharmacokinetics and metabolism of both epirubicin (EPI) and verapamil (VPL) to explore the possible pharmacokinetic interactions between these two drugs. Ten patients with advanced breast cancer were given EPI (40 mg/m² in a daily i.v. bolus for 3 consecutive days), and five of them also received VPL (4×120 mg/daily p.o. for 4 consecutive days). The data indicated a significant interaction between these two drugs that affected their metabolism. The areas under the concentration-time curves (AUC) obtained for epirubicin glucuronide, epirubicinol glucuronide, and both of the 7-deoxy-aglycones were higher in the EPI+VPL group as compared with the EPI group. The AUC, terminal half-life, mean residence time, volume of distribution at steady state, and plasma clearance of EPI alone as compared with EPI+VPL did not differ significantly. These results suggest either an induction of enzymes necessary for drug metabolism or an increase in the liver blood flow, resulting in an enhanced generation of metabolites with time or in an inhibition of excretion processes. Comparisons of the AUC values obtained for EPI and its metabolites after the first, second, and third injections of EPI revealed a cumulative effect for the metabolites that was more pronounced in the EPI+VPL group, being significant (P<0.05) for epirubicin glucuronide in both treatment groups and for epirubicinol glucuronide in the EPI+VPL group. Maximal concentrations of VPL and nor-VPL reached 705±473 and 308±122 ng/ml, respectively, with the steady-state concentrations being 265±42 ng/ml for VPL and 180±12 ng/ml for nor-VPL.This study was supported by the Erich und Gertrud Roggenbuck-Stiftung zur Förderung der Krebsforschung (Hamburg). The anthracycline metabolites were kindly provided by Dr. A. Suarato (Farmitalia, Milano, Italy); nor verapamil was provided by Dr. Traugott (Knoll, Ludwigshafen, Germany)     

Langstrecken-Intensivtransport der Bundeswehr

Zusammenfassung Die Teilnahme der Bundeswehr an internationalen Missionen erfordert ein an die Bedingungen militärischer Einsätze angepasstes Konzept zur intensivmedizinischen Repatriierung. Die umfassende Transportkapazität des auf den Airbus A-310 gestützten Systems von bis zu 44 liegenden Patienten bedingte bereits mehrfach den Einsatz im Rahmen ziviler Großschadensereignisse. Der Transport der häufig vital gefährdeten Patienten erfordert sowohl eine dem Inlandsstandard anzupassende medizintechnische Ausstattung der Luftfahrzeuge als auch entsprechend qualifiziertes medizinisches Begleitpersonal, das aufgrund der Sitzplätze zahlenmäßig begrenzt ist. Dieser Umstand verlangt vom Personal Umsicht bei der Betreuung von zeitgleich mehreren Patienten sowie Befähigung zum eigenständigen Arbeiten. Die Patienten-Transport-Einheiten (PTE) entsprechen in der technischen Ausstattung dem Intensivbehandlungsplatz einer modernen Klinik und gewährleisten auch über eine längere Transportzeit eine Intensivtherapie auf höchstem Niveau. Die Arbeit mit dieser Ausrüstung, die Besonderheiten des Langstreckenlufttransportes und die spezielle Situation des militärischen Einsatzes stellen zusätzliche Anforderungen an das Personal. Um dem gerecht zu werden, erfolgt, ergänzend zur täglichen Arbeit im Rettungsdienst, in den Notaufnahmen und auf den Intensivstationen der Bundeswehrkrankenhäuser eine spezielle Schulung von Rettungsassistenten und Ärzten am Flugmedizinischen Institut der Luftwaffe.     

What therapeutic benefits are there in the early diagnosis of metastases in patients with breast carcinoma?]

Early detection and curative treatment of metastasis of breast cancer is seldom. Local surgery and radiation could be helpful. The survival time was sometimes not a psychological advantage for the patients with early detection of metastasis.     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.     

Translocation (2;4)(p23;q25) An additional case of a new recurrent anomaly in acute myeloid leukemia

A second case of acute myeloid leukemia (AML) with a t(2;4)(p23;q25) as the sole anomaly is reported. Our case had a de novo AML (M2); the case previously described had AML (M2) post-MDS. It is suggested that t(2;4)(p23;q25) is a new, recurrent, but rare anomaly in AML.