Metabolic Fate of Clonidine. (V): Metabolism of Clonidine after Subcutaneous Administration of Clonidine to Rats, Dogs and Monkeys and Dermal Application of Clonidine Tape, M-5041T, to Rats.

Yamahata, Tohru; Minaki, Yasuo; Okada, Shigeya; Kohno, Ryuichi; Nishikawa, Hitoshi; Esumi, Yoshio; Jin, Yoshitaka; Okamura, Yosuke; Ishizaki, Masao; Gunji, Shinobu; Muto, Hiromi; Taguchi, Manami; Ninomiya, Shinichi

doi:10.2133/dmpk.11.411

Cited by 3 publications

(1 citation statement)

References 4 publications

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“…In order to collect preliminary data on the course of the metabolism process and the structures of metabolites formed by the selected for comparison pharmaceutical substances, a detailed review of the available literature was performed [36,46,[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63].…”

Section: Preliminary Characterization Of Metabolism Pathwaysmentioning

confidence: 99%

Photocatalysis as a Tool for in Vitro Drug Metabolism Simulation: Multivariate Comparison of Twelve Metal Oxides on a Set of Twenty Model Drugs

2019

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The constant development in the area of medicinal substances on the market and their subsequent progress in the field of drug analysis has become one of the reasons for the search for alternative, cheaper, and faster methods to determine the metabolism pathways of new molecular entities (NMEs). The simulation of transformation processes using photocatalysis is considered to be one of the promising methods. Although its effectiveness has been proven, the research has so far focused especially on titanium dioxide, while a more accurate comparison of the suitability of different photocatalysts in terms of their use in drug metabolism studies has not been performed. For this purpose, a set of twelve metal oxides was prepared and their photocatalytic efficiency in the direction of drug metabolism mimicking was checked on a model mixture of twenty medicinal substances differing both in chemical structure and pharmacological properties. Incubation with human liver microsomes (HLMs) was used as the reference method. The metabolic profiles obtained with the use of LC-MS analysis were compared using multidimensional chemometric techniques; and the graphic presentation of the results in the form of PCA plot and cluster dendrogram enabled their detailed interpretation and discussion. All tested photocatalysts confirmed their effectiveness. However, the exact outcome of the study indicate advantage of the WO3-assisted photocatalysis over other metal oxides.

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Section: Preliminary Characterization Of Metabolism Pathwaysmentioning

confidence: 99%

Photocatalysis as a Tool for in Vitro Drug Metabolism Simulation: Multivariate Comparison of Twelve Metal Oxides on a Set of Twenty Model Drugs

2019

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Metabolic Fate of Clonidine. (III): Absorption, Distribution and Excretion in Rats after Repeated Subcutaneous Administration of Clonidine.

Yamahata

Minaki

Nishikawa

et al. 1996

Drug Metabolism and Pharmacokinetics

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Summary: After repeated subcutaneous administration of 14C-clonidine to male rats once a day for 21 days at a dose of 1 mg/kg/day, the absorption, distribution and excretion of radioactivity were investigated .1. No marked variation was observed in the radioactivity level of the plasma at every 24 hr after daily ad ministration. After the final dosing, the elimination of radioactivity from the plasma after 24 hr was slower than that after single dosing.2. The radioactivity levels in most tissues at 24 hr after daily administration achieved nearly a steady state by the 21st dosing, but the level in aorta increased cumulatively and the value was 10 times higher than that after the first dosing. After the final dosing, the elimination of radioactivity from the tissues after 24 hr was slower than that after single dosing. On the whole body autoradiograms, high radioactivity was also found in the gastro-intestinal content, some exocrine glands and nasal cavity.3. The total excretion of radioactivity in the urine and feces during each 24 hr after daily dosing was almost constant after the 2nd dosing and 71.6 and 26.4% of the cumulative dose were excreted in the urine and feces, respectively, within 168 hr after the final dosing.

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Metabolic Fate of Clonidine. (IV): Plasma Protein Binding of Clonidine In vitro and In vivo and Transfer to Fetus and Milk in Rats after Subcutaneous Administration of Clonidine.

Yamahata

Minaki

Nishikawa

et al. 1996

Drug Metabolism and Pharmacokinetics

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Summary: The plasma protein binding of 14C-clonidine in vitro and in vivo and its transfer into the fetus and milk in rats were investigated.1. The binding ratios of radioactivity in vitro to male rat, dog, monkey and human plasma proteins did not change with drug concentration in any species and no marked species difference was observed, however, in vivo binding to male rat, dog and monkey plasma proteins tended to increase with the elapse of time.2. After subcutaneous administration to pregnant rats at a dose of 1 mg/kg, the radioactivity levels in the fetal kidney and liver were higher than that in the maternal plasma. The radioactivity was rapidly elimi nated from the fetal tissues as that from the maternal plasma. On the whole body autoradiograms, compara ble radioactivity was found in the fetus with the maternal plasma.3. The radioactivity level in the milk reached a maximum at 30 min after subcutaneous administration at a dose of 1 mg/kg, being 5.5 times higher than that in the plasma, but was comparable with that in the plasma after 8 hr and decreased to undetectable level at 72 hr after administration.

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Metabolic Fate of Clonidine. (V): Metabolism of Clonidine after Subcutaneous Administration of Clonidine to Rats, Dogs and Monkeys and Dermal Application of Clonidine Tape, M-5041T, to Rats.

Cited by 3 publications

References 4 publications

Photocatalysis as a Tool for in Vitro Drug Metabolism Simulation: Multivariate Comparison of Twelve Metal Oxides on a Set of Twenty Model Drugs

Photocatalysis as a Tool for in Vitro Drug Metabolism Simulation: Multivariate Comparison of Twelve Metal Oxides on a Set of Twenty Model Drugs

Metabolic Fate of Clonidine. (III): Absorption, Distribution and Excretion in Rats after Repeated Subcutaneous Administration of Clonidine.

Metabolic Fate of Clonidine. (IV): Plasma Protein Binding of Clonidine In vitro and In vivo and Transfer to Fetus and Milk in Rats after Subcutaneous Administration of Clonidine.

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