Desirable pharmacokinetic properties of13C-uracil as a breath test probe of gastric emptying in comparison with13C-acetate and13C-octanoate in rats

Sugiyama, Erika; Inada, Makoto; Kunizaki, Jun-ichi; Tobita, Kazuki; Yoshida, Takahito; Kashimoto, Minoru; Hirao, Yukihiro; Sato, Hitoshi

doi:10.1080/00365520903114904

Cited by 3 publications

(1 citation statement)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use of 13 C-labeled probes for assessment of in vivo metabolic activity has been extensively studied by our research group. 16,[21][22][23] In particular, we have demonstrated the utility of the 13 C-EM breath test for the quick and noninvasive evaluation of CYP3A-mediated drug interactions in vivo. 16 As summarized in Table 4, the AUCs of the 13 C breath response decreased by approximately half in the CBD-NE coadministration groups (10 and 50 mg/kg) compared with the control, indicating suppression of 13 C-EM metabolism due to CBD-mediated inhibition of CYP3A.…”

mentioning

confidence: 99%

Nonlinear Disposition and Metabolic Interactions of Cannabidiol Through CYP3A Inhibition In Vivo in Rats

Nagao

Nakano

Tajima

et al. 2020

Cannabis and Cannabinoid Research

Self Cite

View full text Add to dashboard Cite

Introduction: Cannabidiol (CBD) is known to affect the pharmacokinetics of other drugs through metabolic inhibition of CYP2C19 and CYP3A4. However, there is a lack of in vivo evidence for such drug interactions. Therefore, we investigated the saturability of CBD metabolism and CBD-drug interactions through inhibition of CYP3A in vivo. Materials and Methods: A nanoemulsion formulation of CBD (CBD-NE) was orally administered to rats at doses of 5, 10, 25, and 50 mg/kg, and plasma concentrations of CBD were measured by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to examine the dose-dependency of CBD exposure (area under the curve [AUC]). To examine the effect of a CYP3A inhibitor on CBD pharmacokinetics, rats were orally pretreated with 50 mg/kg ketoconazole (KCZ), a strong CYP3A inhibitor, before oral administration of CBD-NE at doses of 10 and 50 mg/kg, and plasma concentrations of CBD were measured using LC-MS/MS. Moreover, 13 C-erythromycin was orally administered following administration of either NE (without CBD), as a control, or CBD-NE at 1, 10, and 50 mg/kg, and 13 C-breath response was measured by using an infrared analyzer. Results: After administration of various doses of the nanoemulsified CBD formulation to rats, the exposure of CBD (i.e., the AUC calculated from the plasma concentration-time profile) increased in a greater than doseproportional manner, especially at doses above 10 mg/kg. The AUC and maximum plasma concentration (C max) of CBD after oral administration of CBD-NE (10 mg/kg) increased approximately three times by the coadministration of KCZ. Moreover, according to the CBD-induced changes of 13 C-breath response, the metabolism of 13 C-erythromycin was shown to be inhibited by CBD at doses of 10 and 50 mg/kg, but not at 1 mg/kg. Conclusions: Nonlinear disposition and CYP-mediated drug interactions of CBD at doses exceeding 10 mg/kg were demonstrated for the first time in vivo in rats. Given the present results, it is proposed that caution for dosedependent drug interactions should be considered for CBD.

show abstract

mentioning

confidence: 99%