Population pharmacokinetics of blonanserin in Chinese healthy volunteers and the effect of the food intake

Yao, Wen; Shang, Dewei; Xie, He-Zhi; Wang, Xipei; Ni, Xiao; Zhang, Ming; Lu, Wei; Qiu, Chen; Liu, Xia; Li, Fangfang; Li, Xuan; Luo, Fengming

doi:10.1002/hup.2290

Cited by 10 publications

(9 citation statements)

References 13 publications

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“…Due to high variability in the absorption rate constant under fasted conditions, the model event time (MTIME) was used to describe the absorption rate constant (Yang et al ., ). Comparing the MTIME method to other current methods (Yun et al ., ; Wen et al ., ), which screen the food effect covariate, the MTIME method in the present study has favorable properties, including a low RSE(%) of parameter, and enhanced bootstrap and VPC. We therefore selected the MTIME method for modeling the food effect of PK of mosapride.…”

Section: Discussionmentioning

confidence: 90%

Determination of influence of food intake after a single oral dose of mosapride in beagle dogs using nonlinear mixed effect modeling

Chae

Hwang

Baek

et al. 2015

Vet Pharm & Therapeutics

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The objective of this study was to describe the population pharmacokinetics (PK) of mosapride under fasting and fed conditions. A single 5-mg oral dose of mosapride was administered to fasted (n = 15) and fed (n = 12) beagle dogs. Plasma concentrations of mosapride were subsequently measured by liquid chromatography-tandem mass spectrometry. Data were analyzed using modeling approaches with the NONMEM 7.2 software. A one-compartment open PK model utilizing model event time (MTIME) with first-order absorption and first-order elimination was found to be more appropriate than all other PK models tested. The absorption rate constants of mosapride were significantly decreased under fed conditions, compared to fasting conditions. The observed bootstrap medians of PK parameters were generally consistent with the corresponding population mean estimates. Furthermore, with the exception of some mosapride concentrations, most of observed data fell into the range of the 5th and 95th percentiles of the simulated values. Overall, the final model was able to describe the observed mosapride concentrations reasonably well. These findings suggest that food intake affects both the rate and extent of absorption of mosapride and that the pharmacological effect of mosapride can differ significantly depending on food intake.

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Section: Discussionmentioning

confidence: 90%

Determination of influence of food intake after a single oral dose of mosapride in beagle dogs using nonlinear mixed effect modeling

Chae

Hwang

Baek

et al. 2015

Vet Pharm & Therapeutics

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“…Food intake affected absorption and relative bioavailability but not clearance, so did not cause drug accumulation. 6 According to FDA guidelines, the 90% CIs of the ratios of AUC and C max obtained after drug administration under fasting and fed studies are used to evaluate the impact of meals. Food effect was deemed to be significant, as in bioequivalence analyses, if the AUC ratio (fed:fasted) was more than 1.25 or less than 0.8.…”

Section: Discussionmentioning

confidence: 99%

“…4 The terminal half-life of the analyte in the plasma (t 1/2 ) after a single dose is approximately 12 hours, and repeated dosing has no significant effect on t 1/2 . 6 There are numerous factors that can influence the pharmacokinetics (PKs) of blonanserin in vivo, including food, alcohol, and grapefruit juice, which considerably enhance exposure to blonanserin and its metabolites. Grapefruit juice also increases the bioavailability of blonanserin, which may reduce the rate of systemic clearance.…”

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confidence: 99%

Bioequivalence of Blonanserin Tablets Under Fasting and Fed Conditions in Healthy Chinese Subjects

Lei,

Yan,

et al. 2023

Clinical Pharm in Drug Dev

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Blonanserin is a novel oral antischizophrenic drug. Under fasting (n = 50) and fed (n = 60) conditions, this study compared the bioequivalence of the generic blonanserin tablet with the reference blonanserin tablet. In this single‐center, randomized, open‐label, 2‐period, 2‐sequence, crossover study, 110 patients were randomly given a 4‐mg dose of either the test or reference blonanserin tablet with a 14‐day washout period. Blood samples were taken before performing and up to 72 hours following. A validated high‐performance liquid chromatography‐tandem mass spectrometry technique was used to measure the levels of blonanserin in plasma. Safety was evaluated throughout the study. The study found no significant differences in the maximum observed drug concentration in the plasma (Cmax), the area under the plasma concentration‐time curve from time 0 to the last sampling time (AUC0‐t), and the area under the plasma concentration‐time curve from time 0 to infinity (AUC0‐∞) between the 2 blonanserin formulations. The 90% confidence intervals of the geometric mean ratio of the test/reference formulations for Cmax, AUC0‐t, and AUC0‐∞ were within the 80%‐125% limit. Food dramatically raised blonanserin exposure, and also significantly prolonged the lag time of absorption. No serious adverse events occurred. These results indicate that the 2 blonanserin formulations were bioequivalent and well tolerated in healthy Chinese subjects. In clinical treatment, it is necessary to consider the food effect of blonanserin.

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“…To our knowledge, there has been no report as to the efficacy of blonanserin in the treatment of neurosyphilis. Blonanserin is a novel atypical antipsychotic drug which was approved for treatment of schizophrenia within the dose range of 8–24 mg/day in Japan and Korea [ 16 , 17 ]. It has been shown to have potent antagonistic properties at dopamine D 2 and serotonin 5-HT 2 A receptors, and is effective in alleviating positive and negative symptoms of schizophrenia [ 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

Psychotic mania as the solitary manifestation of neurosyphilis

et al. 2018

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BackgroundNeurosyphilis remains a diagnostic challenge in current psychiatric practice because of its pleomorphic psychiatric manifestations. Although neurosyphilis can present with a wide range of psychiatric symptoms, psychotic mania as its solitary manifestation is an unusual phenomenon.Case presentationA 46-year-old man, with no history of any psychiatric disorder, exhibited abruptly developed symptoms of psychotic mania. He was admitted to a psychiatric ward for further evaluation and treatment. Upon admission, his cognitive function was unimpaired, and the hyperactivity was not severe. Also, no abnormalities were found upon neurological examination and brain magnetic resonance imaging. He was initially diagnosed as bipolar disorder with psychotic features. On the 3rd day after admission, he was confirmed as having neurosyphilis by analysis of cerebrospinal fluid and treated with intravenous penicillin—in combination with blonanserin—an atypical antipsychotic drug. After 2 weeks of treatment, most of the symptoms had abated.ConclusionsThe present case emphasizes that patients presenting with atypical psychiatric manifestation should be screened for possible syphilis, particularly in the absence of previous psychiatric history, and suggests that combination of blonanserin with antibiotic therapy may be effective in the treatment of the manic and psychotic symptoms secondary to neurosyphilis.

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Population pharmacokinetics of blonanserin in Chinese healthy volunteers and the effect of the food intake

Abstract: This is the first study assessing the PK profile of blonanserin with population PKs method. The results can be used for simulation in further clinical trial and optimize individual dosage regimens using a Bayesian methodology in patients.

Cited by 10 publications

References 13 publications

Determination of influence of food intake after a single oral dose of mosapride in beagle dogs using nonlinear mixed effect modeling

Determination of influence of food intake after a single oral dose of mosapride in beagle dogs using nonlinear mixed effect modeling

Bioequivalence of Blonanserin Tablets Under Fasting and Fed Conditions in Healthy Chinese Subjects

Psychotic mania as the solitary manifestation of neurosyphilis

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