An <i>in vitro</i> interethnic comparison of monoamine oxidase activities between Japanese and Caucasian livers using rizatriptan, a serotonin receptor 1B/1D agonist, as a model drug

Iwasa, Takashi; Sano, Hitoshi; Uchiyama, Naotaka; Hara, Kazushi; Okochi, Hitoshi; Nakagawa, Kazuo; Yasumori, Toshio; Ishizaki, Tomoko

doi:10.1046/j.1365-2125.2003.01922.x

Cited by 11 publications

(8 citation statements)

References 34 publications

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“…As above mentioned, CYP1A2 metabolism is less susceptible to ethnic differences. As for MAO activity, limited data are available on any ethnic differences in intestinal and hepatic MAO distribution, although Iwasa et al demonstrated that the hepatic MAO‐A and B activities in Japanese do not differ from or are fairly close to those in Caucasians. Therefore, low oral bioavailability potential contribution to ethnic difference in rasagiline PK is limited.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and safety of single and multiple doses of rasagiline in healthy Japanese and caucasian subjects

Elgart

Rabinovich‐Guilatt

Eyal

et al. 2018

Basic Clin Pharma Tox

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As of March 2018, rasagiline is approved for the treatment of Parkinson disease in 55 countries including Japan. The present study evaluated the pharmacokinetics (PK) and safety of rasagiline in healthy Japanese and Caucasian subjects following single and multiple administrations of three rasagiline doses. In this double-blind, placebo-controlled study, 64 healthy subjects (32 Japanese and 32 Caucasian) received either rasagiline (0.5, 1.0, or 2.0 mg) or placebo for 10 days with PK sampling for single-dose administration on day 1 and for multiple administration on day 10. Regardless of administration schedule, rasagiline plasma concentrations and dose-related increases in exposure parameters were similar between Japanese and Caucasians. Rasagiline accumulation (2-fold for 0.5 mg and 3-fold for 1.0 mg and 2.0 mg doses) following multiple administration was similar across the ethnic groups. Geometric mean ratios (GMR) comparing Japanese to Caucasians for AUC , C and AUC following single administration were 1.38, 1.17 and 1.38 for 0.5 mg; 1.22, 1.20 and 1.22 at 1.0 mg; and 1.02, 1.00 and 1.02 at for 2.0 mg. GMR for AUC and C following multiple administration were 1.43 and 1.06 at 0.5 mg, 1.06 and 1.00 at 1.0 mg, and 1.09 and 1.07 at 2.0 mg. Safety measures were unremarkable and similar between Caucasian and Japanese subjects. Comparable systemic exposure and safety parameters were demonstrated for rasagiline administered to healthy Japanese and Caucasian subjects.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and safety of single and multiple doses of rasagiline in healthy Japanese and caucasian subjects

Elgart

Rabinovich‐Guilatt

Eyal

et al. 2018

Basic Clin Pharma Tox

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“…Almotriptan and zolmitriptan are metabolized by MAO and multiple CYPs, with the involvement of CYP1A2 [523,524]. Rizatriptan is mainly metabolized by MAO-A via oxidative deamination [525]. Propranolol, but not metoprolol and nadolol, increased its AUC by 70% through MAO-A inhibition [526].…”

Section: Anti-migraine Drugsmentioning

confidence: 98%

Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development

Zhou¹,

Zhou²,

Liu³

et al. 2009

CMC

149

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Cytochrome P450 2C9 (CYP2C9) is one of the most abundant CYP enzymes in the human liver. CYP2C9 metabolizes more than 100 therapeutic drugs, including tolbutamide, glyburide, diclofenac, celecoxib, torasemide, phenytoin losartan, and S-warfarin). Some natural and herbal compounds are also metabolized by CYP2C9, probably leading to the formation of toxic metabolites. CYP2C9 also plays a role in the metabolism of several endogenous compounds such as steroids, melatonin, retinoids and arachidonic acid. Many CYP2C9 substrates are weak acids, but CYP2C9 also has the capacity to metabolise neutral, highly lipophilic compounds. A number of ligand-based and homology models of CYP2C9 have been reported and this has provided insights into the binding of ligands to the active site of CYP2C9. Data from the site-directed mutagenesis studies have revealed that a number of residues (e.g. Arg97, Phe110, Val113, Phe114, Arg144, Ser286, Asn289, Asp293 and Phe476) play an important role in ligand binding and determination of substrate specificity. The resolved crystal structures of CYP2C9 have confirmed the importance of these residues in substrate recognition and ligand orientation. CYP2C9 is activated by dapsone and its analogues and R-lansoprazole in a stereo-specific and substrate-dependent manner, probably through binding to the active site and inducing positive cooperativity. CYP2C9 is subject to induction by rifampin, phenobarbital, and dexamethasone, indicating the involvement of pregnane X receptor, constitutive androstane receptor and glucocorticoid receptor in the regulation of CYP2C9. A number of compounds have been found to inhibit CYP2C9 and this may provide an explanation for some clinically important drug interactions. Tienilic acid, suprofen and silybin are mechanism-based inhibitors of CYP2C9. Given the critical role of CYP2C9 in drug metabolism and the presence of polymorphisms, it is important to identify drug candidates as potential substrates, inducer or inhibitors of CYP2C9 in drug development and drug discovery scientists should develop drugs with minimal interactions with this enzyme. Further studies are warranted to explore the molecular determinants for ligand-CYP2C9 binding and the structure-activity relationships.

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“…Gómez et al (1988) demonstrated the presence of MAO-A and MAO-B activity in rat liver microsomes using enzyme-specific substrates and inhibitors and changes in temperature and pH sensitivity that were similar to those in mitochondria. Iwasa et al (2003) found that MAO activity for the metabolism of rizatriptan was similar between the microsomal and mitochondrial fractions of Japanese liver donors. In the present study, microsomal MAO activity seems to be qualitatively similar to that in the mitochondrial preparation.…”

Section: O Glucmentioning

confidence: 91%

In Vitro Metabolism of the Analgesic Bicifadine in the Mouse, Rat, Monkey, and Human

Erickson

Hollfelder²,

Tenge³

et al. 2007

Drug Metab Dispos

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ABSTRACT:The in vitro metabolism of [ 14 C]bicifadine by hepatic microsomes and hepatocytes from mouse, rat, monkey, and human was compared using radiometric high-performance liquid chromatography and liquid chromatography/tandem mass spectrometry. Two main metabolic pathways were identified in all four species. One pathway was an NADPH-dependent pathway in which the methyl group was oxidized to form a hydroxymethyl metabolite (M2). Its formation was inhibited in human microsomes only by quinidine, a CYP2D6 inhibitor. In incubations with individual cDNA-expressed human cytochromes P450, M2 was formed only by CYP2D6 and CYP1A2, with CYP2D6 activity 6-fold greater than that of CYP1A2.

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An in vitro interethnic comparison of monoamine oxidase activities between Japanese and Caucasian livers using rizatriptan, a serotonin receptor 1B/1D agonist, as a model drug

Cited by 11 publications

References 34 publications

Pharmacokinetics and safety of single and multiple doses of rasagiline in healthy Japanese and caucasian subjects

Pharmacokinetics and safety of single and multiple doses of rasagiline in healthy Japanese and caucasian subjects

Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development

In Vitro Metabolism of the Analgesic Bicifadine in the Mouse, Rat, Monkey, and Human

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