Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In Vitro
Flucloxacillin (FLU), an isoxazolyl penicillin, is widely used for the treatment of different bacterial infections in intensive care units (ICU). Being highly bound to plasma proteins, FLU is prone to drug-drug interactions (DDI) when administered concurrently with other drugs. As FLU is binding to...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/9/6/309 |
| _version_ | 1827715422591385600 |
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| author | Maximilian Stolte Weaam Ali Janne Jänis Andre’ Gessner Nahed El-Najjar |
| author_facet | Maximilian Stolte Weaam Ali Janne Jänis Andre’ Gessner Nahed El-Najjar |
| author_sort | Maximilian Stolte |
| collection | DOAJ |
| description | Flucloxacillin (FLU), an isoxazolyl penicillin, is widely used for the treatment of different bacterial infections in intensive care units (ICU). Being highly bound to plasma proteins, FLU is prone to drug-drug interactions (DDI) when administered concurrently with other drugs. As FLU is binding to both Sudlow’s site I and site II of human serum albumin (HSA), competitive and allosteric interactions with other drugs, highly bound to the same sites, seem conceivable. Knowledge about interaction(s) of FLU with the widely used anticancer agents paclitaxel (PAC), imatinib (IMA), and 5-fluorouracil (5-FU is scarce. The effects of the selected anticancer agents on the unbound fraction of FLU were evaluated in pooled plasma as well as in HSA and α-1-acid glycoprotein (AGP) samples, the second major drug carrier in plasma. FLU levels in spiked samples were analyzed by LC-MS/MS after ultrafiltration. Significant increase in FLU unbound fraction was observed when in combination with PAC and IMA and to a lesser extent with 5-FU. Furthermore, significant binding of FLU to AGP was observed. Collectively, this is the first study showing the binding of FLU to AGP as well as demonstrating a significant DDI between PAC/IMA/5-FU and FLU. |
| first_indexed | 2024-03-10T19:17:51Z |
| format | Article |
| id | doaj.art-5084f6ceab7f476297a700b6041c8634 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T19:17:51Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-5084f6ceab7f476297a700b6041c86342023-11-20T03:11:22ZengMDPI AGAntibiotics2079-63822020-06-019630910.3390/antibiotics9060309Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In VitroMaximilian Stolte0Weaam Ali1Janne Jänis2Andre’ Gessner3Nahed El-Najjar4Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, GermanyInstitute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, GermanyDepartment of Chemistry, University of Eastern Finland, FI-80100 Joensuu, FinlandInstitute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, GermanyInstitute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, GermanyFlucloxacillin (FLU), an isoxazolyl penicillin, is widely used for the treatment of different bacterial infections in intensive care units (ICU). Being highly bound to plasma proteins, FLU is prone to drug-drug interactions (DDI) when administered concurrently with other drugs. As FLU is binding to both Sudlow’s site I and site II of human serum albumin (HSA), competitive and allosteric interactions with other drugs, highly bound to the same sites, seem conceivable. Knowledge about interaction(s) of FLU with the widely used anticancer agents paclitaxel (PAC), imatinib (IMA), and 5-fluorouracil (5-FU is scarce. The effects of the selected anticancer agents on the unbound fraction of FLU were evaluated in pooled plasma as well as in HSA and α-1-acid glycoprotein (AGP) samples, the second major drug carrier in plasma. FLU levels in spiked samples were analyzed by LC-MS/MS after ultrafiltration. Significant increase in FLU unbound fraction was observed when in combination with PAC and IMA and to a lesser extent with 5-FU. Furthermore, significant binding of FLU to AGP was observed. Collectively, this is the first study showing the binding of FLU to AGP as well as demonstrating a significant DDI between PAC/IMA/5-FU and FLU.https://www.mdpi.com/2079-6382/9/6/309albuminα-1-acid glycoproteindrug-drug interactionsanti-infective agentsultrafiltrationcancer |
| spellingShingle | Maximilian Stolte Weaam Ali Janne Jänis Andre’ Gessner Nahed El-Najjar Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In Vitro Antibiotics albumin α-1-acid glycoprotein drug-drug interactions anti-infective agents ultrafiltration cancer |
| title | Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In Vitro |
| title_full | Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In Vitro |
| title_fullStr | Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In Vitro |
| title_full_unstemmed | Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In Vitro |
| title_short | Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In Vitro |
| title_sort | paclitaxel imatinib and 5 fluorouracil increase the unbound fraction of flucloxacillin in vitro |
| topic | albumin α-1-acid glycoprotein drug-drug interactions anti-infective agents ultrafiltration cancer |
| url | https://www.mdpi.com/2079-6382/9/6/309 |
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