Multiple-dose pharmacokinetics of epirubicin at four different dose levels: studies in patients with metastatic breast cancer

Summary Pharmacokinetic analysis of epirubicin and its metabolites epirubicinol and 7-deoxy-13-dihydro-epirubicinol aglycone during the first and the fourth courses of treatment was performed in 78 patients with metastatic breast cancer. The patients were treated every 3 weeks with epirubicin given as 10-min i.v. infusions at four different dose levels: 40, 60, 90 and 135 mg/m². In most cases (76 of 78 cases), plasma concentration-time curves fitted to a three-compartmental pharmacokinetic model. The terminal half-life of epirubicin was independent of dose and duration of treatment. Large interindividual differences were demonstrated (meant _1/2, 21.6±7.9 h; range, 10.6–69 h;n=110). In two subjects, extremely long half-lives and high serum bilirubin concentrations indicated impaired liver function. No correlation was found between the half-life and levels of liver alanine aminotransferase (ALAT) or serum creatinine. The metabolite epirubicinol appeared quickly after epirubicin administration and its half-lives were shorter than that of the parent compound (meant _1/2, 18.1±4.8 h; range, 8.2–38.4 h;n=105).Formation of the aglycone metabolite was delayed and the half-life of this metabolite was shorter than that of epirubicin (meant _1/2, 13±4.6 h; range, 2.7–29 h;n=104). The AUC of epirubicin and the total AUC (drug and metabolites) were linearly proportional to the dose, with the former value constituting two-thirds of the latter. A correlation was found between AUC and the plasma concentration of epirubicin at two time points (2 and 24 h after administration). The proposed model was AUC=9.44×c ₂+62.5×c ₂₄+157.7 (r=0.953).This work was supported by the Lundbeck Foundation, the Michaelsen Foundation and Farmitalia Carlo Erba Ltd.     

Tele-monitoring of home blood pressure in treated hypertensive patients

AIM: To compare the accuracy of clinic blood pressure (CBP) and telemedical home blood pressure (HBP) measurement in the assessment of antihypertensive effect. METHODS: 362 patients on antihypertensive medication performed HBP measurement (5 days, duplicate measurements, four times daily) and ambulatory blood pressure (ABP) monitoring in random order. Main outcome measure was the agreement of CBP and HBP with daytime ABP. RESULTS: CBP was much higher than ABP and average HBP (p < 0.001). There was a progressive decline in HBP over the course of the study, achieving the level of daytime ABP on the last 2 monitoring days. The correlation between CBP and ABP was weak (systolic: r = 0.343, diastolic r = 0.430), whereas strong correlations existed between HBP and ABP (systolic r = 0.804, diastolic r = 0.776). A progressive improvement in the strength of the correlation between average HBP of single days and ABP was obtained over the 5 monitoring days. The HBP readings taken in the afternoon showed a stronger correlation with ABP than the values measured in the morning, at noon and in the evening. Averaging more HBP readings taken on succeeding days resulted in a progressive improvement in the agreement with ABP with a further benefit when readings of day 1 were included. CONCLUSIONS: The accuracy of telemedical HBP measurement is substantially better than that of CBP. The results suggest, that HBP should be measured for 5 days, and afternoon measurements should be preferred in assessing control of hypertension.     

Sentinel Lymph Node Dissection in Locally Recurrent Breast Cancer

Annals of Surgical Oncology - The aim of this study was to investigate the use of sentinel lymph node dissection (SLND) in the treatment of patients with locally recurrent breast cancer. A total of...     

Validity of a questionnaire survey: response patterns in different subgroups and the effect of social desirability

Questionnaire surveys are often used in epidemiology and survey research. However, investigations have shown that the method suffers from biases. If the intention is to examine differences between subgroups in a sample, studies have shown that people tend to give answers to questionnaires more according to a social norm than to the actual situation. This has been called social desirability. The aim of this study was to investigate response bias in subgroups of a sample in a large questionnaire survey (n = 9,200) and to study whether social desirability has an impact on survey results in dental research. The answers were divided into subgroups according to gender, age, and residence and were compared with corresponding data from dental insurance claims. The levels of agreement were found to vary considerably and the differences were highly statistically significant. The variation in agreement showed that bias on the group level increased when the distance from an anticipated social norm was larger. This implies that the divergence from a socially desirable mode of action influences the magnitude of the bias.