Biomimetic Oxidation of Denaverine Hydrochloride

Smolinka, Kai; Göber, Berthold

doi:10.1002/(sici)1099-0690(199903)1999:3<679::aid-ejoc679>3.0.co;2-w

Cited by 6 publications

(1 citation statement)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Por outro lado, existem relativamente poucos trabalhos na literatura que abordem a oxidação de drogas e fármacos por estes sistemas biomiméticos. Alguns exemplos incluem praziquantel (MELO et al, 2005), lidocaína, odapipam, ABT-200, ABT-418 e aminopirina (CARRIER;BATTIONI;MANSUY, 1993;CHORGHADE et al, 1996), acetaminofeno (BERNADOU et al, 1991VIDAL et al, 1993), denaverina (SMOLINKA; GOBER, 1999), dentre outros (BALOGH; KESERU, 2004).…”

Section: Metaloporfirinas Sintéticas Como Modelo Para O Estudo De Metunclassified

Lychnophora ericoides' Mart: avaliação farmacológica e considerações sobre o metabolismo oxidativo das substâncias bioativas

Santos¹,

Lopes²

View full text Add to dashboard Cite

Section: Metaloporfirinas Sintéticas Como Modelo Para O Estudo De Metunclassified

Lychnophora ericoides' Mart: avaliação farmacológica e considerações sobre o metabolismo oxidativo das substâncias bioativas

Santos¹,

Lopes²

View full text Add to dashboard Cite

Biomimetic Chemical Catalysts in the Oxidative Activation of Drugs

2004

View full text Add to dashboard Cite

show abstract

In vitro liver metabolism of aclidinium bromide in preclinical animal species and humans: Identification of the human enzymes involved in its oxidative metabolism

Albertí

Sentellas

Salvà

2011

Biochemical Pharmacology

View full text Add to dashboard Cite

. In vitro liver metabolism of aclidinium bromide in preclinical animal species and humans: identification of the human enzymes involved in its oxidative metabolism. Biochemical Pharmacology, Elsevier, 2011, 81 (6) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 AbstractThe metabolism of aclidinium bromide, a novel long-acting antimuscarinic drug for the maintenance treatment of chronic obstructive pulmonary disorder, has been investigated in liver microsomes and hepatocytes of mice, rats, rabbits, dogs, and humans. Due to the rapid hydrolysis of this ester compound, two distinct radiolabeled forms of aclidinium were studied. The main biotransformation route of aclidinium was the hydrolytic cleavage of the ester moiety, resulting in the formation of the alcohol metabolite (M2, LAS34823) and carboxylic acid metabolite (m3, LAS34850) , which mainly occurred non-enzymatically. By comparison, the oxidative metabolism was substantially lower and the metabolite profiles were similar across all five species examined. Aclidinium was metabolized oxidatively to four minor primary metabolites that were identified as monohydroxylated derivatives of aclidinium at the phenyl (M4) and glycolyl (m4, m6 and m7) moieties of the molecule. The NADPH-dependent metabolite m4 involved the loss of one of the thiophene rings of aclidinium.Incubations with human recombinant P450 isoforms and inhibition studies with selective chemical inhibitors and antibodies of human P450 enzymes demonstrated that the oxidative metabolism of aclidinium is primarily mediated by CYP3A4 and CYP2D6. Additionally, up to eight secondary metabolites were also characterized, involving further hydrolysis, oxidation, or glucuronidation of the primary metabolites.Also, the liver oxidative metabolism of the alcohol metabolite (LAS34823) resulted in the production of one hydroxylated metabolite (M1) mediated by human CYP2D6, whereas the acid metabolite (LAS34850) was not metabolized enzymatically, although a minor non-enzymatic and NADPH-dependent reduction was observed.

show abstract

Biomimetic Oxidation of Denaverine Hydrochloride

Abstract: The behavior of denaverine (1) in various chemical model systems based on metalloporphyrins as catalysts was investigated to determine the possible oxidative metabolism. The resulting derivatives were compared to a biological model system and in vivo metabolism in rat and human.

Cited by 6 publications

References 12 publications

Lychnophora ericoides' Mart: avaliação farmacológica e considerações sobre o metabolismo oxidativo das substâncias bioativas

Lychnophora ericoides' Mart: avaliação farmacológica e considerações sobre o metabolismo oxidativo das substâncias bioativas

Biomimetic Chemical Catalysts in the Oxidative Activation of Drugs

In vitro liver metabolism of aclidinium bromide in preclinical animal species and humans: Identification of the human enzymes involved in its oxidative metabolism

Contact Info

Product

Resources

About