Pharmacokinetic and pharmacodynamic profile of bendamustine and its metabolites.
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Darwish M, Bond M, Hellriegel E, Robertson P Jr, Chovan JP
Pharmacokinetic and pharmacodynamic profile of bendamustine and its metabolites.
Cancer Chemother Pharmacol. 2015 Jun;75(6):1143-54. doi: 10.1007/s00280-015-2727-6. Epub 2015 Apr 1.
- PubMed ID
- 25829094 [ View in PubMed]
- Abstract
PURPOSE: Bendamustine is a unique alkylating agent indicated for the treatment of chronic lymphocytic leukemia and rituximab-refractory, indolent B cell non-Hodgkin's lymphoma. Despite the extensive experience with bendamustine, its pharmacokinetic profile has only recently been described. This overview summarizes the pharmacokinetics, pharmacokinetic/pharmacodynamic relationships, and drug-drug interactions of bendamustine in adult and pediatric patients with hematologic malignancies. METHODS: A literature search and data on file (including a human mass balance study, pharmacokinetic population analyses in adult and pediatric patients, and modeling analyses) were evaluated for inclusion. RESULTS: Bendamustine concentrations peak at end of intravenous infusion (~1 h). Subsequent elimination is triphasic, with the intermediate t 1/2 (~40 min) as the effective t 1/2 since the final phase represents <1 % of the area under the curve. Bendamustine is rapidly hydrolyzed to monohydroxy-bendamustine and dihydroxy-bendamustine, which have little or no activity. Cytochrome P450 (CYP) 1A2 oxidation yields the active metabolites gamma-hydroxybendamustine and N-desmethyl-bendamustine, at low concentrations, which contribute minimally to cytotoxicity. Minor involvement of CYP1A2 in bendamustine elimination suggests a low likelihood of drug-drug interactions with CYP1A2 inhibitors. Systemic exposure to bendamustine 120 mg/m(2) is comparable between adult and pediatric patients; age, race, and sex have been shown to have no significant effect on systemic exposure in either population. The effect of hepatic/renal impairment on bendamustine pharmacokinetics remains to be elucidated. Higher bendamustine concentrations may be associated with increased probability of nausea or infection. No clear exposure-efficacy response relationship has been observed. CONCLUSIONS: Altogether, the findings support dosing based on body surface area for most patient populations.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Famotidine Cytochrome P450 1A2 Protein Humans NoInhibitorDetails - Drug Reactions
Reaction Details Details Details Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareBendamustineFluvoxamine The serum concentration of Bendamustine can be increased when it is combined with Fluvoxamine. BendamustineEnoxacin The serum concentration of Bendamustine can be increased when it is combined with Enoxacin. BendamustineRofecoxib The serum concentration of Bendamustine can be increased when it is combined with Rofecoxib. BendamustineCiprofloxacin The serum concentration of Bendamustine can be increased when it is combined with Ciprofloxacin. BendamustineQuinidine The serum concentration of Bendamustine can be increased when it is combined with Quinidine.
