Relevant pharmacological interactions between alkylating agents and antiepileptic drugs : Preclinical and clinical data
Copyright © 2021 Elsevier Ltd. All rights reserved..
Seizures are relatively common in cancer patients, and co-administration of chemotherapeutic and antiepileptic drugs (AEDs) is highly probable and necessary in many cases. Nonetheless, clinically relevant interactions between chemotherapeutic drugs and AEDs are rarely summarized and pharmacologically described. These interactions can cause insufficient tumor and seizure control or lead to unforeseen toxicity. This review focused on pharmacokinetic and pharmacodynamic interactions between alkylating agents and AEDs, helping readers to make a rational choice of treatment optimization, and thus improving patients' quality of life. As an example, phenobarbital, phenytoin, and carbamazepine, by increasing the hepatic metabolism of cyclophosphamide, ifosfamide and busulfan, yield smaller peak concentrations and a reduced area under the plasma concentration-time curve (AUC) of the prodrugs; alongside, the maximum concentration and AUC of their active products were increased with the possible onset of severe adverse drug reactions. On the other side, valproic acid, acting as histone deacetylase inhibitor, showed synergistic effects with temozolomide when tested in glioblastoma. The present review is aimed at providing evidence that may offer useful suggestions for rational pharmacological strategies in patients with seizures symptoms undertaking alkylating agents. Firstly, clinicians should avoid the use of enzyme-inducing AEDs in combination with alkylating agents and prefer the use of AEDs, such as levetiracetam, that have a low or no impact on hepatic metabolism. Secondly, a careful therapeutic drug monitoring of both alkylating agents and AEDs (and their active metabolites) is necessary to maintain therapeutic ranges and to avoid serious adverse reactions.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:175 |
|---|---|
| Enthalten in: |
Pharmacological research - 175(2022) vom: 06. Jan., Seite 105976 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Cucchiara, Federico [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Alkylating Agents |
|---|
| Anmerkungen: |
Date Completed 18.03.2022 Date Revised 18.03.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.phrs.2021.105976 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM333230094 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM333230094 | ||
| 003 | DE-627 | ||
| 005 | 20231225221228.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.phrs.2021.105976 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1110.xml |
| 035 | |a (DE-627)NLM333230094 | ||
| 035 | |a (NLM)34785318 | ||
| 035 | |a (PII)S1043-6618(21)00560-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Cucchiara, Federico |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Relevant pharmacological interactions between alkylating agents and antiepileptic drugs |b Preclinical and clinical data |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.03.2022 | ||
| 500 | |a Date Revised 18.03.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Seizures are relatively common in cancer patients, and co-administration of chemotherapeutic and antiepileptic drugs (AEDs) is highly probable and necessary in many cases. Nonetheless, clinically relevant interactions between chemotherapeutic drugs and AEDs are rarely summarized and pharmacologically described. These interactions can cause insufficient tumor and seizure control or lead to unforeseen toxicity. This review focused on pharmacokinetic and pharmacodynamic interactions between alkylating agents and AEDs, helping readers to make a rational choice of treatment optimization, and thus improving patients' quality of life. As an example, phenobarbital, phenytoin, and carbamazepine, by increasing the hepatic metabolism of cyclophosphamide, ifosfamide and busulfan, yield smaller peak concentrations and a reduced area under the plasma concentration-time curve (AUC) of the prodrugs; alongside, the maximum concentration and AUC of their active products were increased with the possible onset of severe adverse drug reactions. On the other side, valproic acid, acting as histone deacetylase inhibitor, showed synergistic effects with temozolomide when tested in glioblastoma. The present review is aimed at providing evidence that may offer useful suggestions for rational pharmacological strategies in patients with seizures symptoms undertaking alkylating agents. Firstly, clinicians should avoid the use of enzyme-inducing AEDs in combination with alkylating agents and prefer the use of AEDs, such as levetiracetam, that have a low or no impact on hepatic metabolism. Secondly, a careful therapeutic drug monitoring of both alkylating agents and AEDs (and their active metabolites) is necessary to maintain therapeutic ranges and to avoid serious adverse reactions | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Antiepileptic drugs | |
| 650 | 4 | |a Busulfan | |
| 650 | 4 | |a CYP enzymes | |
| 650 | 4 | |a Cancer therapy | |
| 650 | 4 | |a Cyclophosphamide | |
| 650 | 4 | |a Drug-drug Interactions | |
| 650 | 4 | |a Ifosfamide | |
| 650 | 4 | |a Nitrosoureas | |
| 650 | 4 | |a Temozolomide | |
| 650 | 4 | |a Thiotepa | |
| 650 | 7 | |a Alkylating Agents |2 NLM | |
| 650 | 7 | |a Anticonvulsants |2 NLM | |
| 700 | 1 | |a Ferraro, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Luci, Giacomo |e verfasserin |4 aut | |
| 700 | 1 | |a Bocci, Guido |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Pharmacological research |d 1992 |g 175(2022) vom: 06. Jan., Seite 105976 |w (DE-627)NLM012597384 |x 1096-1186 |7 nnns |
| 773 | 1 | 8 | |g volume:175 |g year:2022 |g day:06 |g month:01 |g pages:105976 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.phrs.2021.105976 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 175 |j 2022 |b 06 |c 01 |h 105976 | ||