Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker.
Cancer Chemother Pharmacol
; 86(4): 535-545, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32948918
ABSTRACT
PURPOSE:
Carboplatin dose is calculated based on kidney function, commonly estimated with imperfect creatinine-based formulae. Iohexol is used to measure glomerular filtration rate (GFR) and allows calculation of a more appropriate carboplatin dose. To address potential concerns that iohexol administered during a course of chemotherapy impacts that therapy, we performed in vitro and in vivo pharmacokinetic drug-drug interaction evaluations of iohexol.METHODS:
Carboplatin was administered IV to female mice at 60 mg/kg with or without iohexol at 300 mg/kg. Plasma ultrafiltrate, kidney and bone marrow platinum was quantitated by atomic absorption spectrophotometry. Paclitaxel microsomal and gemcitabine cytosolic metabolism as well as metabolism of CYP and UGT probes was assessed with and without iohexol at 300 µg/mL by LC-MS/MS.RESULTS:
In vivo carboplatin exposure was not significantly affected by iohexol co-administration (platinum AUC combination vs alone plasma ultrafiltrate 1,791 vs 1920 µg/mL min; kidney 8367 vs 9757 µg/g min; bone marrow 12.7 vs 12.7 µg/mg-protein min). Paclitaxel microsomal metabolism was not impacted (combination vs alone 6-α-OH-paclitaxel 38.3 versus 39.4 ng/mL/60 min; 3-p-OH-paclitaxel 26.2 versus 27.7 ng/mL/60 min). Gemcitabine human cytosolic elimination was not impacted (AUC combination vs gemcitabine alone dFdU 24.1 versus 23.7 µg/mL/30 min). Iohexol displayed no relevant inhibition of the CYP and UGT enzymes in human liver microsomes.CONCLUSIONS:
Iohexol is unlikely to affect the clinical pharmacokinetics of carboplatin, paclitaxel, gemcitabine, or other agents used in combination with carboplatin treatment. Measuring GFR with iohexol to better dose carboplatin is unlikely to alter the safety or efficacy of chemotherapy through pharmacokinetic drug-drug interactions.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Iohexol
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Protocolos de Quimioterapia Combinada Antineoplásica
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Carboplatina
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Meios de Contraste
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos