A Strömgren

Aarhus University Hospital, Århus, Central Jutland, Denmark

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Publications (4)11.18 Total impact

  • A S Strömgren, B T Sørensen, P Jakobsen, A Jakobsen
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    ABSTRACT: A limited sampling method for estimation of the etoposide area under the curve (AUC) is presented. The method was developed and validated in 23 patients (42 pharmacokinetic studies) with small-cell lung cancer (SCLC), limited disease. The patients received 100 mg/m2 etoposide as a 90-min intravenous infusion in combination with carboplatin, allowing for etoposide dose modification at a following course (25% increase or decrease) due to high or low nadir values for leukocytes or thrombocytes. Of the 42 pharmacokinetic studies, 27 were used in the model development and 15 were used in the model validation. Single regression analyses of the AUC versus the fitted concentrations for the model data set were performed at several time points. The analyses demonstrated high and essentially identical correlation coefficients in the interval between 2 and 21 h, with a maximal value of 0.96 being recorded at 4 h. Multiple regression analysis was then performed using fitted concentrations corresponding to 0.08-21 h. The best model for one sample was AUC = 1.01 x (dose level divided by 100 mg/m2) + 799 x C4 h, that for two samples was AUC = 1.43 x (dose level divided by 100 mg/m2) + 544 x C4 h + 1756 x C21 h, and that for three samples was AUC = 0.07 x (dose level divided by 100 mg/m2) + 110 x C5 min + 474 x C4 h + 1759 x C21 h. Not unexpectedly, the model validation revealed that the one-sample model was less precise than the two- or three-sample model [percentage of root mean squared error (RMSE%) = 11.6%, 7.1%, and 5.4%, respectively]. All models proved to be unbiased in the validation [percentage of mean predictive error (MPE%) +/- SE = 4.2% +/- 11.0%, 7.9% +/- 6.1%, and 6.3% +/- 5.3%, respectively]. The models were subsequently validated in 14 pharmacokinetic studies of patients with metastatic germ-cell tumours who were receiving combination chemotherapy with cisplatin and bleomycin plus 100 mg/m2 etoposide as a 90-min infusion. The RMSE% was 13.4%, 10.8%, and 9.0% and the MPE% +/- SE was -1.0% +/- 11.9%, 1.7% +/- 10.5%, and 2.7% +/- 7.9% for the one-, two-, and three-sample models, respectively. The limited sampling methods presented herein may prove to be a most valuable tool for therapeutic drug monitoring in regimens in which etoposide is given in combination with carboplatin or with cisplatin and bleomycin.
    Cancer Chemotherapy and Pharmacology 02/1993; 32(3):226-30. · 2.80 Impact Factor
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    ABSTRACT: A limited sampling method for estimation of the carboplatin area under the curve (AUC) from one or two plasma concentration determination is presented. The model was conceived and developed using 43 pharmacokinetic studies in 15 patients with ovarian cancer (model data set) who received carboplatin in combination with cyclophosphamide. Linear regression analyses comparing the AUC and the drug concentration at a single time point (0.25-10 h after the end of the infusion) as calculated from the fitted exponential equations gave correlation coefficients as high as 0.97, with maximal correlations falling within the interval of 2-3.25 h. The model was validated prospectively in 9 patients with ovarian cancer (validation data set) who received the same treatment as did the model data set (21 pharmacokinetic studies), testing the equation AUC = 0.52 x C2.75 h + 0.92. Observed and estimated AUCs were correlated in the validation data set (r = 0.91). The mean predictive error (MPE% +/- SE) was -4.4% +/- 3.1% and the root mean squared error (RMSE%) was 13.9%. Multiple regression analysis revealed that adding a second sample drawn at 0.25 h (AUC = 0.053 x C0.25h + 0.401 x C2.75h + 0.628) improved the MPE% to -2.2% +/- 2.1% and the RMSE% to 9.4% (r = 0.96). We conclude that the carboplatin AUC can be estimated from a single plasma sample at 2.75 h or, more precisely, from two plasma samples at 0.25 and 2.75 h. The methods described may prove to be a handy tool for the calculation of approximate AUCs in trials of a size that would discourage detailed pharmacokinetic studies.
    Cancer Chemotherapy and Pharmacology 02/1993; 31(4):324-7. · 2.80 Impact Factor
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    ABSTRACT: The mechanism for renal handling of carboplatin was studied in 17 ovarian cancer patients treated with a combination of carboplatin and cyclophosphamide. Carboplatin and [51Cr]-ethylenediaminetetraacetic acid (EDTA) renal clearances were measured simultaneously during short intervals of from 45 to 120 min. A total of 131 clearance intervals were analyzed during 35 chemotherapy courses. The carboplatin/[51Cr]-EDTA clearance ratio (R) served as an indicator of the net tubular reabsorption (R less than 1) or secretion (R greater than 1). The R value was calculated for each sampling interval. No significant difference was found between interpatient and intertreatment variation. The intertreatment variation as tested against the variation in the short intervals by an F-test was highly significant. We calculated the average R value for each treatment and consequently based our results on a total of 35 observations. The mean R value was 0.77 (t-test for R = 1; P less than 0.001). We conclude that the renal elimination of carboplatin takes place by glomerular filtration followed by tubular reabsorption.
    Cancer Chemotherapy and Pharmacology 02/1992; 30(4):317-20. · 2.80 Impact Factor
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    ABSTRACT: A study was undertaken to examine the relationships between carboplatin's pharmacokinetic parameters and the myelotoxicity associated with its administration in combination with cyclophosphamide. An additional aim of the study was to test the applicability of the method proposed by Calvert et al. for calculation of the carboplatin dose to be used in the combination regimen. A total of 24 previously untreated ovarian cancer patients were given a combination of 250-500 mg/m2 carboplatin and 500 mg/m2 cyclophosphamide every 4 weeks for 4 months. The pharmacokinetics of carboplatin and the associated myelotoxicity were investigated in 64 courses. The results showed a significant correlation (r = 0.89) between the AUC calculated for carboplatin and that predicted according to Calvert's formula [carboplatin dose in milligrams = AUC (glomerular filtration rate +25)]. We conclude that the model is a useful guide in the calculation of the carboplatin dose to be given in combination with cyclophosphamide, and it enables a more precise prediction of the carboplatin exposure than does the conventional calculation, which is based on milligrams of drug per square meter of body surface. The AUC for carboplatin was a reliable predictor of the myelotoxicity as measured by the relative decrease in thrombocyte count. However, the relationship between AUC and myelotoxicity changed during the treatment because of increasing bone marrow toxicity. Despite this finding, dose calculation based on carboplatin's AUC appears to provide an improvement in the clinical use of the drug, and the method also seems to be fully applicable in combination chemotherapy with cyclophosphamide.
    Cancer Chemotherapy and Pharmacology 02/1991; 28(5):397-401. · 2.80 Impact Factor

Publication Stats

91 Citations
11.18 Total Impact Points

Institutions

  • 1991–1993
    • Aarhus University Hospital
      • Department of Oncology
      Århus, Central Jutland, Denmark
  • 1992
    • Aarhus University
      • Department of Oncology
      Aars, Region North Jutland, Denmark