Minimal biliary excretion and enterohepatic recirculation of metoclopramide in patients with extrahepatic cholestasis

Hellstern, A; Hellenbrecht, D.; Saller, Reinhard; Gatzen, M.; Achtert, G.; Brockmann, Pablo E.; Hausleiter, H. J.

doi:10.1007/bf00315511

Cited by 5 publications

(4 citation statements)

References 9 publications

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“…In addition or as an alternative explanation of dicontinuous plasma levels the pH partitioning of MCL into the gastric juice may be dis cussed [ 16]. A third possibility, enterohepatic recirculation of MCL, may be ruled out based on former studies [17]. The wide variation of the plasma concentrations seen in our study has also been observed by others [18][19][20].…”

Section: Pharmacokinetics O F Oral Medium-dosed M Clsupporting

confidence: 62%

Oral Medium-Dosed Metoclopramide versus Placebo as Highly Effective Antiemetic Prophylaxis in In- and Outpatients on Noncisplatin Chemotherapy

Vogt¹,

Hellenbrecht

Saller

et al. 1993

Oncology

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The antiemetic effect of oral medium-dosed metoclopramide (MCL, 3.5 mg/kg b.w./cycle) and placebo for chemotherapy-induced emesis of a noncisplatin regimen was assessed for inpatients and outpatients in two double-blind placebo-controlled sequential analyses according to Bross (1952). MCL was given in 5 single doses of 0.7 mg/kg b.w. at 0 h (loading) and at 2 h (i.e. start of chemotherapy) and 6,10 and 14 h (as maintenance doses). Both studies ended after 8 sequential pairs in favor of MCL (2Α = 2Β = 0.05). Major antiemetic protection ( < 2 emetic episodes per 26 h) was achieved for 8/8 of inpatients and 7/8 of outpatients (placebo 0/8 and 0/8). Side effects neither required discontinuation of the antiemetic regimen nor additional therapy. The median of MCL plasma levels ranged from 150 to 750 ng/ml and terminal half-lives from 3.9 to 8.9 h.

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Section: Pharmacokinetics O F Oral Medium-dosed M Clsupporting

confidence: 62%

Oral Medium-Dosed Metoclopramide versus Placebo as Highly Effective Antiemetic Prophylaxis in In- and Outpatients on Noncisplatin Chemotherapy

Vogt¹,

Hellenbrecht

Saller

et al. 1993

Oncology

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“…As it has been shown that the N-O-glucuronide was also a major metabolite of metoclopramide in the urine [17], it can be assumed that part of the radioactivity excreted into urine was in the form of the 11 C-labeled N-Oglucuronide of [ 11 C]metoclopramide. The visibility of the gall bladder and duodenum on the PET images indicated that [ 11 C]metoclopramide also underwent, to a lower extent, biliary excretion [18].…”

Section: Discussionmentioning

confidence: 99%

Human Biodistribution and Radiation Dosimetry of the P-Glycoprotein Radiotracer [11C]Metoclopramide

et al. 2021

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Purpose To assess in healthy volunteers the whole-body distribution and dosimetry of [11C]metoclopramide, a new positron emission tomography (PET) tracer to measure P-glycoprotein activity at the blood-brain barrier. Procedures Ten healthy volunteers (five women, five men) were intravenously injected with 387 ± 49 MBq of [11C]metoclopramide after low dose CT scans and were then imaged by whole-body PET scans from head to upper thigh over approximately 70 min. Ten source organs (brain, thyroid gland, right lung, myocardium, liver, gall bladder, left kidney, red bone marrow, muscle and the contents of the urinary bladder) were manually delineated on whole-body images. Absorbed doses were calculated with QDOSE (ABX-CRO) using the integrated IDAC-Dose 2.1 module. Results The majority of the administered dose of [11C]metoclopramide was taken up into the liver followed by urinary excretion and, to a smaller extent, biliary excretion of radioactivity. The mean effective dose of [11C]metoclopramide was 1.69 ± 0.26 μSv/MBq for female subjects and 1.55 ± 0.07 μSv/MBq for male subjects. The two organs receiving the highest radiation doses were the urinary bladder (10.81 ± 0.23 μGy/MBq and 8.78 ± 0.89 μGy/MBq) and the liver (6.80 ± 0.78 μGy/MBq and 4.91 ± 0.74 μGy/MBq) for female and male subjects, respectively. Conclusions [11C]Metoclopramide showed predominantly renal excretion, and is safe and well tolerated in healthy adults. The effective dose of [11C]metoclopramide was comparable to other 11C-labeled PET tracers.

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“…The latter mechanism may be responsible for the high plasma concentration at 24 h in GD1 cattle in our study. concentration at 24 h after IV administration in GD1 cattle compared to WT cattle may cause an increase in the enterohepatic [28,32] or gasteroenteric circulation of metoclopramide [33].…”

Section: Discussionmentioning

confidence: 99%

Cytochrome P450 2D14 (CYP2D14) Gene Deletion Variants in the Japanese Black Cattle and Characterization of their Effects on Metoclopramide Pharmacokinetics

Hamamoto¹,

Mizuno²

2015

J Veterinar Sci Technol

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The frequency of cytochrome P450 2D14 (CYP2D14) genetic polymorphisms and their effects on CYP2D14mediated metabolism have not been reported in cattle. Genetic polymorphisms of the CYP2D14 gene in 57 Japanese Black (JB) cattle were determined by polymerase chain reaction (PCR)-direct sequencing. Two types of CYP2D14 gene deletion variants (GD), GD1 and GD2, were observed in this study. The CYP2D6 deletion reportedly results in delayed metabolism of metoclopramide in human. To investigate the effects of CYP2D14 gene deletion in JB cattle, the GD1, GD2 and wild-type (WT) cattle were administered metoclopramide by an intravenous or oral route. Plasma concentrations of metoclopramide in GD1 cattle were significantly higher 24 hour (h) after intravenous administration (P<0.01) and within 1 h after oral administration of metoclopramide compared to levels in GD2 and WT cattle (P<0.01). The half-life at γ-phase (γHL) of metoclopramide after intravenous administration was significantly higher in GD1 compared to WT cattle (P<0.05). Moreover, the elimination rate constant (K 10 ) of GD1 after oral administration of metoclopramide was significantly higher in GD1 compared to WT animals (P<0.05). These results suggest that the higher plasma concentration of metoclopramide in GD1 cattle is caused by delayed metabolism of metoclopramide, owing to CYP2D14 enzyme deficiency.

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Minimal biliary excretion and enterohepatic recirculation of metoclopramide in patients with extrahepatic cholestasis

Cited by 5 publications

References 9 publications

Oral Medium-Dosed Metoclopramide versus Placebo as Highly Effective Antiemetic Prophylaxis in In- and Outpatients on Noncisplatin Chemotherapy

Oral Medium-Dosed Metoclopramide versus Placebo as Highly Effective Antiemetic Prophylaxis in In- and Outpatients on Noncisplatin Chemotherapy

Human Biodistribution and Radiation Dosimetry of the P-Glycoprotein Radiotracer [11C]Metoclopramide

Cytochrome P450 2D14 (CYP2D14) Gene Deletion Variants in the Japanese Black Cattle and Characterization of their Effects on Metoclopramide Pharmacokinetics

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