The concomitant use of lapatinib and paracetamol - the risk of interaction

Karbownik, Agnieszka; Szałek, Edyta; Sobańska, Katarzyna; Grabowski, Tomasz; Klupczynska, Agnieszka; Plewa, Szymon; Wolc, Anna; Magiera, Magdalena; Porażka, Joanna; Kokot, Zenon J.; Grześkowiak, Edmund

doi:10.1007/s10637-018-0573-1

Cited by 7 publications

(8 citation statements)

References 24 publications

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“…Karbownik A. et al study aimed to explore the effect of lapatinib oral administration on the pharmacokinetics of paracetamol, its glucuronidation, and sulfation in rats [43]. In addition, they analyzed the changes of lapatinib pharmacokinetics parameters after concomitant administration with paracetamol.…”

Section: Pharmacokinetics Preclinical Studiesmentioning

confidence: 99%

Modern Instrumental Methods for Qualitative and Quantitative Analysis of Lapatinib in Biological Fluids and Dosage Forms (Review)

2022

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Lapatinib is a small molecule, a heterocyclic quinazoline derivative. The drug is used for targeted therapy of patients with breast cancer, in which there is overexpression of the human epidermal growth factor receptors (HER/ErbB). This review is devoted to studying modern instrumental methods of qualitative and quantitative analysis of lapatinib, which can be used both for quality control and standardization (of bulk pharmaceuticals and dosage forms) and pharmacokinetics studies of a drug. Reverse-phase high-performance liquid chromatography (RP-HPLC) is mainly used to identify lapatinib in tablets. Depending on the purpose of the study, various detectors are used (ultraviolet or diode-matrix detector), which makes it possible to determine not only the native compound but also the products of its degradation. Definition of lapatinib in the presence of degraded products is necessary for forced degradation studies to determine drug stability. When a drug is being developed, it is important to define and understand its pharmacokinetics. For such studies, high-performance liquid chromatography (HPLC) coupled with the mass selective detector is often used. It allows determining lapatinib in biological fluids. However, these methods are not applicable for identifying the drug directly in dosage forms and require further development and validation.

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Section: Pharmacokinetics Preclinical Studiesmentioning

confidence: 99%

Modern Instrumental Methods for Qualitative and Quantitative Analysis of Lapatinib in Biological Fluids and Dosage Forms (Review)

2022

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“…In the I S+PA group we also observed increased C max and AUC 0-∞ of paracetamol sulphate by 2.1-and 2.7-fold, respectively with a simultaneous increase in paracetamol sulphate/paracetamol ratio for C max and AUC 0-∞ (p = 0.0003 and p = 0.0003, respectively). Karbownik et al [36][37][38] conducted an in vivo study and proved that other TKIs, i.e. erlotinib, lapatinib and sunitinib significantly affected the PK of paracetamol.…”

Section: The Influence Of Sorafenib On the Pharmacokinetics Of Paracementioning

confidence: 99%

“…Karbownik et al examined the influence of paracetamol on the pharmacokinetics of lapatinib and erlotinib [36,37]. The co-administration of lapatinib and paracetamol increased the AUC 0-t and C max of lapatinib by 240% (p = 0.0030) and by 184% (p = 0.0011), respectively.…”

Section: The Influence Of Paracetamol On the Pharmacokinetics Of Soramentioning

confidence: 99%

In vivo assessment of the drug interaction between sorafenib and paracetamol in rats

Karbownik

Sobańska

Grabowski

et al. 2020

Cancer Chemother Pharmacol

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Purpose Sorafenib is a multi-targeted tyrosine kinase inhibitor (TKI) used for the treatment of advanced renal cell carcinoma, hepatocellular carcinoma and radioactive iodine resistant thyroid carcinoma. Neoplastic diseases are the cause of pain, which may occur regardless of the stage of the disease. Paracetamol is a non-opioid analgesic used alone or in combination with opioids for the treatment of cancer pain. Numerous studies have pointed out changes in the pharmacokinetic parameters of TKIs when co-administered with paracetamol. The aim of the study was to assess drug-drug interactions (DDIs) between sorafenib and paracetamol. Methods Rats were divided into three groups, each consisting of eight animals. The first group received sorafenib (II S), the second group received sorafenib + paracetamol (I S+PA), whereas the third group received only paracetamol (III PA). A single dose of sorafenib (100 mg/kg b.w.) and paracetamol (100 mg/kg b.w.) was administered orally. The plasma concentrations of sorafenib and its metabolite-N-oxide as well as paracetamol and its glucuronide and sulphate metabolites were measured using validated high-performance liquid chromatography (HPLC) method with ultraviolet detection. Results The co-administration of sorafenib and paracetamol increased the maximum concentration (C max) of paracetamol by 33% (p = 0.0372). In the I S+ PA group the C max of paracetamol glucuronide was reduced by 48% (p = < 0.0001), whereas the C max of paracetamol sulphate was higher by 153% (p = 0.0012) than in the III PA group. Paracetamol increased sorafenib and sorafenib N-oxide C max by 60% (p = 0.0068) and 83% (p = 0.0023), respectively. Conclusions A greater knowledge of DDI between sorafenib and paracetamol may help adjust dose properly and avoid toxicity effects in individual patients.

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“…Acetaminophen (Paracetamol) is a common antipyretic /analgesic drug which is easily obtained over-thecounter (OTC). It is metabolized by CPY3A4 to Nacetyl-p-benzoquinone imine (NAPQI) in the liver 11 . NAPQI is produced in little amount at therapeutic doses, but overdosing of paracetamol, leads to increased production of NAPQI 11,12 with consequent formation of conjugates with glutathione.…”

Section: Introductionmentioning

confidence: 99%

Hepatotoxicity Effects of Paracetamol-Denik Cleanser® Co-Administration

Obasi

Maagbo²,

Aa³

2023

Univ J Pharm Res

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Aim and Objective: The concurrent use of herbal products with orthodox medicine is on the rise with the risk of herb-drug interaction that could be beneficial or harmful to the body. Paracetamol (acetaminophen) is an anti-pyretic and analgesic drug metabolized by CYP2E1 to give the major hepatotoxin, N-acetyl-p-benzoquinone imine (NAPQI). Denik cleanserâ is an oral herbal preparation from plants part of Occimum grattissimum, Colocynthis citrullus, Khaya ivorensi. The aim of this study was to evaluate the hepatotoxic effects triggered by Denikâ and paracetamol co-administration in rats. The study sought to mimic conventional usage of Denik cleanserâ followed by ingestion of paracetamol, a likely scenario given the popularity of both compounds. Method: Twenty animals were randomly assigned to four groups, the first group (control) received 0.3 mL distilled water, 2nd group received paracetamol 100 mg/kg, 3rd group received Denik cleanserâ2 mL/kg while the 4th group received both paracetamol and Denik cleanserâ at 100 mg/kg and 2 mL/kg daily for 3 days after which biochemical and histological analysis were carried out. Results: From histological analysis revealed that rats that received Denikâ-only and Denikâ/paracetamol (concomitantly) showed markedly distorted liver architecture compared to control indicating toxicity. Similarly, the biochemical analysis results showed a significant (p<0.05) increase in AST and ALT for the Denikâ/paracetamol group compared to the control group indicating a hepatotoxic event. A non-significant increase in ALP and GGT were also observed in the Denik cleanserâ + paracetamol group. Enhanced metabolism of paracetamol by Denik cleanserâ to NAPQI (hepatotoxic metabolite) is indicated as possible mechanism. Conclusion: The results of this study demonstrated the in vivo potential for a herb/drug interaction involving paracetamol and Denik cleanserâ resulting in liver injury.Therefore, caution is strongly advised against its casual, non-medically supervised usage. Peer Review History: Received: 3 November 2022; Revised: 7 December; Accepted: 9 January 2023, Available online: 15 January 2023 Academic Editor: Dr. Nuray Arı, Ankara University, Turkiye, ari@ankara.edu.tr Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Sangeetha Arullappan, Universiti Tunku Abdul Rahman, Malaysia, sangeetha@utar.edu.my Prof. Hüsniye Kayalar, Ege University, Turkey, husniyekayalar@gmail.com Similar Articles: CO-ADMINISTRATION OF GOKO HERBAL CLEANSER AND PARACETAMOL: A HERB-DRUG INTERACTION STUDY IN-VITRO ANTIOXIDANT, LIPID PEROXIDATION INHIBITION AND LIPID PROFILE MODULATORY ACTIVITIES OF HB CLEANSER®BITTERS IN WISTAR RATS

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The concomitant use of lapatinib and paracetamol - the risk of interaction

Cited by 7 publications

References 24 publications

Modern Instrumental Methods for Qualitative and Quantitative Analysis of Lapatinib in Biological Fluids and Dosage Forms (Review)

Modern Instrumental Methods for Qualitative and Quantitative Analysis of Lapatinib in Biological Fluids and Dosage Forms (Review)

In vivo assessment of the drug interaction between sorafenib and paracetamol in rats

Hepatotoxicity Effects of Paracetamol-Denik Cleanser® Co-Administration

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