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Sökning: L773:0959 4973 > Palle Josefine

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1.
  • Palle, Josefine, et al. (författare)
  • Doxorubicin pharmacokinetics is correlated to the effect of induction therapy in children with acute myeloid leukemia
  • 2006
  • Ingår i: Anti-Cancer Drugs. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4973 .- 1473-5741. ; 17:4, s. 385-392
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the pharmacokinetics of doxorubicin in 41 children treated for newly diagnosed acute myeloid leukemia. Doxorubicin, 75 mg/m(2) body surface area, was administered by constant i.v. infusion over 8 h. Four children with Down's syndrome (DS), 1.2-2.3 years old, had a median total body clearance of 523 ml/min/m(2). The median clearance in non-DS children, 0.6-1.8 years old (n=4) and 2.5-17.7 years old (n=33), was 446 and 538 ml/min/m(2), respectively. Patients who went into complete remission (CR) after induction therapy had a significantly higher median plasma concentration of doxorubicin than those who did not, 249 compared with 180 ng/ml, respectively (P=0.036; analysis restricted to non-DS patients). Doxorubicin plasma concentration was an independent factor for CR, both in univariate (P=0.031) and multivariate analysis including sex, age and white blood cell count at diagnosis (P=0.021). Patients who reached CR had a significantly lower doxorubicin clearance than those who did not, 513 and 657 ml/min/m(2), respectively (P=0.017). In conclusion, doxorubicin plasma concentration and total body clearance during up-front treatment were correlated to the effect of induction therapy. Prospective studies should be performed to confirm the concentration-effect relationship and explore the possibility of therapeutic monitoring.
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2.
  • Palle, Josefine, et al. (författare)
  • Etoposide pharmacokinetics in children treated for acute myeloid leukemia
  • 2006
  • Ingår i: Anti-Cancer Drugs. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4973 .- 1473-5741. ; 17:9, s. 1087-1094
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the pharmacokinetics of etoposide in 45 children treated for newly diagnosed acute myeloid leukemia. Etopcoside, 100 mg/m(2) body surface area/24h, was administered by 96-h continuous intravenous infusion. Concomitantly, the children received cytarabine 200 mg/m(2)/24 h by intravenous infusion and 6-thioguanine 100 mg/m(2) twice daily orally. Median total body clearance in children 0.5-11.8 (n=4) and 2.3-17.7 years old (n=36) without Down's syndrome was 17.1 and 17.6 ml/min/m(2), respectively (P=0.96). Five children with Down's syndrome had a median clearance of 13.6 ml/min/m(2) (P=0.067 compared with non-Down's syndrome children). Eighteen of the children received a second identical treatment course 3-4 weeks later; there was a significant correlation between individual clearance values (p=0.56; P=0.017). We found no significant correlation between etoposide pharmacolkinetics and the remission rate or the relapse rate. In conclusion, our findings indicate that special dose-calculation guidelines for infants above 3 months old are not substantiated by age-dependent pharmacolkinetics of etoposide. Down's syndrome children might be candidates for dose reduction if our data are confirmed in larger numbers of patients. Low course-to-course variability indicates that pharmacolkinetically guided dosing of etoposide might be clinically relevant, if larger studies can demonstrate that this approach decreases toxicity or increases response rates.
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3.
  • Palle, Josefine, et al. (författare)
  • Thioguanine pharmacokinetics in induction therapy of children with acute myeloid leukemia
  • 2009
  • Ingår i: ANTI-CANCER DRUGS. - 0959-4973 .- 1473-5741. ; 20:1, s. 7-14
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the pharmacokinetics of 6-thioguanine (6TG) in 50 children treated for newly diagnosed acute myeloid leukemia, four of them with Down syndrome (DS). They received oral 6TG 100 mg/m(2) body surface area twice daily for 4 days. Etoposide, 100 mg/m(2)/24 h, and cytarabine, 200 mg/m(2)/24 h, were administered concomitantly by intravenous infusion. On day 5, doxorubicin 75 mg/m2 was given as an 8-h infusion. The concentration of thioguanine nucleotides (TGN) in erythrocytes, the active metabolites of 6TG, was determined by high-performance liquid chromatography. The mean TGN concentration from 72, 95, and 106-h samples was used as a measure of drug exposure for each individual. The median TGN concentration in non-DS children above 2 years of age was 2.30 mu mol/mmol Hb (range 0.57-25.3). The TGN concentrations varied widely (30-fold) also after dose normalization. We found no correlation with demographic, clinical, or biochemical parameters, and differences in bioavailability might be the most important explanation to interpatient variability. Children with high TGN concentration tended to have longer treatment interval to the next course, but we found no correlation with our predefined parameters for clinical response, that is, remission and relapse rate. Therefore, 6TG does not seem to be a candidate for therapeutic drug monitoring by TGN measurement, at least not in the setting of short multidrug treatment courses. Children with DS had significantly higher TGN concentrations, indicating that dose reduction might be considered to reach the same drug exposure as in non-DS children.
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