Therapeutic drug monitoring and pharmacokinetic compartmental analysis of sulpiride double‐peak absorption profile after oral administration to human volunteers

Helmy, Sally A.

doi:10.1002/bdd.1843

Cited by 23 publications

(10 citation statements)

References 38 publications

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“…After Powders 4 and 5 were administered by intragastric administration, notoginsenoside R 1 and ginsenosides Rg 1 and Rb 1 exhibited double peaks in the C-T gures (Powder 4 was more obvious), which were consistent with results previously reported [21,33]. This result could be due to differential rates of absorption along the gastrointestinal tract, and this prolonged residence time of the drug in the body could be bene cial to the maintenance of the drug effect, but the mechanisms of the double peaks remain to be determined [34,35]. The data suggested that the decrease in particle size can successfully improve the bioavailability within a range of 213.93 ~ 90.38 μm (Powders 1 ~ 4), and the result was not in agreement with the dissolution data (Figure 2a-d).…”

Section: In Vivo Studysupporting

confidence: 89%

Effect of micronization on Panax notoginseng: In vitro dissolution & in vivo bioavailability evaluations

Liang

Xu²,

et al. 2020

Preprint

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Background: Panax notoginseng (PN), the most widely used dietary supplement and herbal in Asian countries. The effect of micronization of PN is not fully clear. The aim of this study was to investigate the effects of the particle size and treatment temperature of Panax notoginseng powder (PNP) and the potential to improve the bioavailability.Methods: Several properties of PNP, including the surface morphology and thermal properties were extensively characterized by scanning electron microscopy (SEM), polarized light microscopy (PLM) and differential scanning calorimetry (DSC). The in vitro release and in vivo bioavailability of Panax notoginseng sapoins (PNS) were investigated by high-performance liquid chromatography (HPLC) and ultra-high-pressure liquid chromatography-MS/MS (UHPLC-MS/MS).Results: The results showed that particle size reduction significantly change the PNS in vitro dissolution and in vivo pharmacokinetic. The PNP with a wide size range (from 60 to 214 μm). Several properties of PNP were extensively characterized, these changes of physicochemical properties of PNP provide a better understanding of the in vitro and in vivo release behaviors of PNS. The in vitro studies demonstrated that the dissolution of PNS and particle size was nonlinear (dose- and size-dependent). The pharmacokinetic parameters of PNP in rats were determined by UHPLC-MS/MS. Powder 4 (90.38 ± 8.28 μm) showed significantly higher AUC0-T values in plasma (P < 0.05). In addition, we also investigated the influence of the hydrothermal treatment of PNP. The results showed that the PNS in vitro release and in vivo bioavailability were highest of PNP pre-treatment at 40°C.Conclusion: The PNP with a particle size around 90 μm and heat pre-treatment at 40°C would be beneficial.

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Section: In Vivo Studysupporting

confidence: 89%

Effect of micronization on Panax notoginseng: In vitro dissolution & in vivo bioavailability evaluations

Liang

Xu²,

et al. 2020

Preprint

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“…The finding that the effects of methylphenidate, which blocks both dopamine and noradrenaline transporters [51,52], were not accompanied by significant effects of the selective D2-receptor antagonist sulpiride is surprising. First, previous research has established that the present dose of sulpiride is effective at approximately 2 hours after intake, indexed in terms of both sulpiride plasma concentrations [40,53] and behavioral effects on reversal learning [54]. Second, the exact same dose of sulpiride did have a significant effect in Westbrook et al [31], where the exact same study protocol was applied.…”

Section: Discussionmentioning

confidence: 93%

Methylphenidate boosts choices of mental labor over leisure depending on baseline striatal dopamine

Hofmans

Papadopetraki²,

Bosch

et al. 2019

Preprint

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The cognitive enhancing effects of methylphenidate are well established, but the mechanisms remain unclear. We recently demonstrated that methylphenidate boosts cognitive motivation by enhancing the weight on the benefits of a cognitive task in a manner that depended on striatal dopamine. Here we considered the complementary hypothesis that methylphenidate might also act by changing the weight on the opportunity cost of a cognitive task. To this end, fifty healthy participants (25 women) completed a novel cognitive effort discounting task that was sensitive to opportunity cost, and required choices between task and leisure. They were tested on methylphenidate, sulpiride or placebo and also underwent an [18F]DOPA PET scan to quantify baseline dopamine synthesis capacity. Methylphenidate boosted choices of cognitive effort over leisure across the group, and this effect was greatest in participants with more striatal dopamine at baseline. The effects of sulpiride did not reach significance. This study strengthens the motivational account of methylphenidate’s effects on cognition and suggests that methylphenidate reduces the cost of mental labor by increasing striatal dopamine.

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“…Aspartate amino transferase transient elevation was reported in one patient in the absorption of eltrombopag occurs along the gastrointestinal tract. 15,16 Enterohepatic circulation could also be a potential mechanism. 17 The plasma exposure (AUC 0-24 h and C max ) of hetrombopag in CITP patients increased greater than dose-proportional over the dose range of 2.5 to 7.5 mg/d, which was consistent with our previous observation in healthy volunteers.…”

Section: Discussionmentioning

confidence: 99%

First‐in‐patient study of hetrombopag in patients with chronic idiopathic thrombocytopenic purpura

Wang

Chen

Zhang

et al. 2020

Journal of Thrombosis and Haemostasis

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Background: Idiopathic thrombocytopenic purpura (ITP) especially refractory and (or) relapsed ITP, is a serious and global health burden and its clinical treatment is far from being satisfied. Hetrombopag is a novel, small-molecule thrombopoietin receptor agonist for the treatment of chronic idiopathic thrombocytopenic purpura (CITP). Objectives: This first-in-patient study aimed to investigate the safety, pharmacokinetics, and anticipated therapeutic dose of hetrombopag in CITP patients. Methods: In this multicenter, first-in-patient study, CITP patients received hetrombopag in a dose escalation (2.5 mg/day, 5 mg/day, or 7.5 mg/day) cohort. All patients received hetrombopag in fasting condition once daily for 2 weeks. Results: Of 44 patients screened, 32 were enrolled and treated. Most adverse events were graded 1 to 2 (ie, mild to moderate), and the incidence and severity were similar for three study cohorts. The pharmacokinetics of hetrombopag were found to be nonlinear with greater than dose-proportional: 12.5% of patients (1/8) in the 2.5 mg/d cohort, 58.3% of patients (7/12) in the 5 mg/d cohort, 66.7% of patients (8/12) in the 7.5 mg/d cohort reached the primary study endpoint of a platelet count exceeding 50 × 10 9 /L on day 28. Conclusion: Hetrombopag was well tolerated and preliminarily efficacious. Efficacy, safety, and pharmacokinetic data suggest that 7.5 mg hetrombopag once daily was the anticipated therapeutic dose of hetrombopag in CITP patients and has been recommended for investigation in a later confirmatory clinical study of hetrombopag.

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Therapeutic drug monitoring and pharmacokinetic compartmental analysis of sulpiride double‐peak absorption profile after oral administration to human volunteers

Cited by 23 publications

References 38 publications

Effect of micronization on Panax notoginseng: In vitro dissolution & in vivo bioavailability evaluations

Effect of micronization on Panax notoginseng: In vitro dissolution & in vivo bioavailability evaluations

Methylphenidate boosts choices of mental labor over leisure depending on baseline striatal dopamine

First‐in‐patient study of hetrombopag in patients with chronic idiopathic thrombocytopenic purpura

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Therapeutic drug monitoring and pharmacokinetic compartmental analysis of sulpiride double‐peak absorption profile after oral administration to human volunteers

Cited by 23 publications

References 38 publications

Effect of micronization on Panax notoginseng: In vitro dissolution &amp; in vivo bioavailability evaluations

Effect of micronization on Panax notoginseng: In vitro dissolution &amp; in vivo bioavailability evaluations

Methylphenidate boosts choices of mental labor over leisure depending on baseline striatal dopamine

First‐in‐patient study of hetrombopag in patients with chronic idiopathic thrombocytopenic purpura

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Effect of micronization on Panax notoginseng: In vitro dissolution & in vivo bioavailability evaluations

Effect of micronization on Panax notoginseng: In vitro dissolution & in vivo bioavailability evaluations