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Background: Although the biological agent ustekinumab (UST) is reported to be effective for Crohn's disease (CD) in pediatric as well as adult patients, data on the efficacy and safety of UST in pediatric patients with CD are limited. Here, we describe the case of a pediatric patient who showed an allergic reaction to UST after subcutaneous (SC) maintenance injections but not immediately after initial intravenous (IV) injection.Case Presentation: A 9-year-old boy presented to our hospital with diarrhea lasting 2 years and weight loss, leading to the diagnosis of CD. After prednisolone (PSL) was tapered and discontinued, he promptly relapsed. According to our institution's protocol, we introduced the biological agent infliximab (IFX) with premedication. Coughing and vomiting was observed after the second dose of IFX and it was changed to adalimumab (ADA). However, the effect of ADA gradually disappeared after 18 months; therefore, it was discontinued and he was treated using UST. The first IV UST dose was given after administering hydrocortisone (HDC), an antiallergic and antipyretic analgesic, as premedication, and no obvious adverse reaction was observed. After 8 weeks, UST was subcutaneously injected without premedication. The patient then complained of nausea, dizziness, and headache within 15 min of UST administration. Therefore, for the third dose of UST, HDC was administered again as premedication. However, nausea, dizziness, and headache presented 10 min after UST administration, resulting in discontinuation of further UST treatment.Conclusion: Careful distinction between “true” infusion-related reactions (IRRs) and anaphylaxis or allergic reactions is necessary to determine whether biological agents can be continued after the development of “so-called” IRRs. For true IRRs, it may be possible to continue using the biological agent with appropriate premedication; however, in cases of anaphylaxis, the biological agent itself should be changed.

Afatinib is an oral tyrosine kinase inhibitor (TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug monitoring (TDM) in clinical settings. This study sought to develop a simple and sensitive competitive enzyme-linked immunosorbent assay (ELISA) to quantify afatinib in plasma for routine pharmacokinetic applications. An anti-afatinib antibody was obtained using (S)-N-4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)-quinazoline-4,6-diamine (CTQD), which has the same substructure as afatinib, as a hapten. Enzyme labeling of afatinib with horseradish peroxidase was similarly performed using CTQD. A simple competitive ELISA for afatinib was developed based on the principle of direct competition between afatinib and the enzyme marker for the anti-afatinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Plasma afatinib concentrations below the limit of quantification of 30 pg/mL were reproducibly measurable. Also, the values of plasma afatinib levels measured from 20 patients were comparable with those measured by high-performance liquid chromatography, and there was a strong correlation between the values determined by both methods (Y = 0.976X – 0.207, r = 0.975). As indicated by its specificity and sensitivity, this newly developed ELISA for afatinib is an important tool for TDM and studies of the pharmacokinetics of afatinib. Keywords: Afatinib, Enzyme-linked immunosorbent assay, Therapeutic drug monitoring, Tyrosine-kinase inhibitor

N-Alkylated oligo- and poly(p-benzamide)s exist as dynamic helical structures with all-cis amide conformation. Imidazole N-alkylated amides also show cis conformational preference, but their major conformer is changed from cis to trans by addition of acid. Here, based on those findings, we designed and synthesized aromatic triamides 3 and hexaamides 4 containing an imidazole ring as candidate foldamers anticipated to exhibit acidinduced conformational change. X-ray structure analysis of oligomer 3c showed that it takes all-cis conformation in the crystal. In solution, all the oligoamides examined existed as an equilibrium mixture of 4 conformers, among which the major conformer was the folded all-cis structure as judged from the low-temperature ¹H NMR spectra. When trifluoroacetic acid-d was added to a solution of the oligoamides in methylene chlorided2, only 2 conformers were observed in the low-temperature ¹H NMR spectra, and the major conformer was the (trans, cis) form with respect to the amide bonds of the imidazole at the 4 and 2 positions. Experimental and theoretical analysis of the CD spectra indicated that the conformation of hexaamides 4 changes upon the addition of acid. Our results suggest that N-alkylated imidazole amide can serve as a key structural motif for the construction of foldamers with acid-switchable conformation. [ABSTRACT FROM AUTHOR]

Background/Aim: Afatinib, a 2nd generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used in treatment of non-small cell lung cancer (NSCLC), causes diarrhoea in over 90% of patients. The association of genetic background with diarrhoea is poorly understood. Patients and Methods: We evaluated the roles of four single nucleotide polymorphisms (SNPs) in ATP binding cassette subfamily B member 1 (ABCB1) and ATP binding cassette subfamily G member 2 (ABCG2) genes–ABCB1 1236 C>T, 2677 G>T/A, and 3435 C>T, and ABCG2 421 C>A–on treatment-induced diarrhoea in 38 patients with NSCLC treated with afatinib. Results: Diarrhoea occurred more frequently in patients with ABCB1 2677 T(A)/T(A) (14/16, 87.5%) than in patients with non-T(A)/T(A) alleles (8/22, 36.4%) (p=0.003). ABCB1 2677 T(A)/T(A) was significantly predictive of diarrhoea (p=0.002) by multivariable regression analysis. Conclusion: Afatinib-induced diarrhoea is associated with the SNP ABCB1 2677 T(A)/T(A). [ABSTRACT FROM AUTHOR]