Impact of nasogastric administration using the simple suspension method on serum tirabrutinib levels: A case report
Hideaki Yashima, Takuya Araki, Akiko Kaneta, Hisashi Takei, Nobuhiko Kobayashi, Yuri Miyazawa, Yoshiyuki Ogawa, Junko Tsukamoto, Hironori Nakamura, Hiroshi Handa, Koujirou YamamotoAbstract
Purpose
Tirabrutinib, an oral Bruton’s tyrosine kinase inhibitor, is used in the treatment of relapsed or refractory primary central nervous system lymphoma (PCNSL) and other B cell malignancies. Although this medication is also administered to older patients, those experiencing dysphagia may require nasogastric administration via a tube. The impact of different administration routes on pharmacokinetics remains a pertinent clinical concern.
Summary
An 82-year-old male patient with relapsed PCNSL initiated tirabrutinib at 320 mg/day under fasting conditions. While the patient was initially able to swallow tablets, progression of dysphagia necessitated a switch to nasogastric administration using the simple suspension method. Serum tirabrutinib concentrations were determined 11 hours after administration by each route using liquid chromatography followed by tandem mass spectrometry and compared. The serum concentration increased from 83.2 ng/mL with oral administration to 191 ng/mL with nasogastric administration, representing an increase of more than 2-fold. The dose, concomitant medications, and sampling conditions were consistent. On day 19, a rash developed that was suspected to be drug induced, prompting discontinuation of tirabrutinib; however, the serum concentration with nasogastric administration was not markedly higher than the previously reported mean 12-hour concentration of around 120 ng/mL. The observed increase in tirabrutinib concentration may primarily reflect enhanced dispersion with the simple suspension method, leading to improved absorption. Potential auxiliary factors, such as changes in absorption rate or inter-individual variability, cannot be excluded. Although a rash occurred, it is unlikely to represent an adverse event due to excessive exposure.
Conclusion
Tirabrutinib concentrations may increase with nasogastric administration using the simple suspension method. In patients unable to ingest tablets orally, careful clinical monitoring is warranted, and therapeutic drug monitoring may be considered in select cases. The accumulation of further cases and pharmacokinetic investigations are warranted.