Population Pharmacokinetics of the BEACOPP Polychemotherapy Regimen in Hodgkin???s Lymphoma and its Effect on Myelotoxicity

Abstract

The results show that the individual pharmacokinetics of BEACOPP drugs are an important link between dosage and toxicity. Accordingly, individualisation of treatment based on pharmacokinetics may result in more uniform toxicity. Individualisation may also allow escalation of the mean dose, which is probably related to better efficacy. As a consequence of the present study, infusion rates should be standardised, and the potential of a dose reduction in the first cycle and of CYP3A4 phenotyping should be addressed in clinical studies.

Population pharmacokinetics of cytarabine, etoposide, and daunorubicin in the treatment for acute myeloid leukemia

“…The importance of kidney function in the dosing of Eto has been shown previously [14][15][16] and was further confirmed in this study with the inclusion of the renal CL-cCrCL relationship. These findings suggest that the dose of Eto should be lowered in patients with poor kidney function, but also that it could be considered to increase the dose in patients with a cCrCL that lies above the normal range.…”

“…Interestingly, a similar effect has been described for Ara-C in a constant infusion regimen [12], whereas other investigators did not find this correlation for patients receiving higher doses of Ara-C (1,000-3,000 mg/m 2 ) [13]. Studies in other types of cancer have shown a correlation between serum creatinine (se-Cr) [14,15] or calculated creatinine clearance (cCrCL) [16] and etoposide PK parameters, thus advocating that kidney function should be considered when dosing etoposide.…”

“…This is in agreement with a study of etoposide phosphate by Kaul et al [36], but the magnitude of the relationship was higher in the present study. Others have not been able to show a correlation between gender and PK parameters [14][15][16]. The clinical relevance of this relationship is diminished by the fact that AUC supposedly is the most important PK parameter for Eto [28,34].…”

Effects of ranolazine in a model of doxorubicin‐induced left ventricle diastolic dysfunction

“…Moreover, pharmacokinetic profiles indicating a possible interaction between ranolazine and doxorubicin at the level of CYP3A and P-glycoprotein (Jerling, 2006;Wilde et al, 2007;Minotti, 2013) prompted us to avoid the concomitant administration of these drugs, in line with the INTERACT study. With this background, the use of ranolazine to target the vicious cycle induced by anthracycline, fuelled by ROS and late I Na appears a reasonable strategy (Figure 8).…”

Pharmacology at Work for Cardio-Oncology: Ranolazine to Treat Early Cardiotoxicity Induced by Antitumor Drugs

“…Ranolazine is a substrate and weak inhibitor of CYP3A enzymes; ranolazine is also a substrate for the drug transporter P-glycoprotein, which is common for drugs that are substrates of CYP3A enzymes (Jerling, 2006). Because metabolization and elimination of anthracyclines or nonanthracycline chemotherapeutics also depend on CYP3A enzymes and P-glycoprotein (Wilde et al, 2007), concomitant administration of ranolazine could change patients' exposure to antitumor drugs. Safety reasons therefore advise not administering ranolazine during chemotherapy.…”