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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. · 2.83 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. · 2.83 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. · 2.83 Impact Factor
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ABSTRACT: At follow-up, 29 young adults treated previously (ages 7-14 years) for nocturnal enuresis by means of conditioning, mostly with a bed alarm, had shown no excess of mental abnormalities, including psychosomatic symptoms. To investigate whether the probands displayed personality traits that could be related to the former enuresis and its treatment, they were asked to answer a mailed questionnaire that attempts to find deviations of personality, the Karolinska Scales of Personality. The scores were compared with those of a group drawn from the general population in the same geographical area and matched for sex and age. The enuresis group was found to have moderately (but significantly) lower scores on socialization and higher scores on suspicion. Possible causes for these findings are discussed. It is concluded that conditioning therapy, which is usually successful in rapidly alleviating enuresis, can also be regarded as a safe treatment. According to this study, it does not seem to leave unwanted aftereffects that could be interpreted as expressions of persisting psychological conflicts.
Acta Psychiatrica Scandinavica 07/1990; 81(6):538-41. · 4.22 Impact Factor
