Metabolism of minaprine in human and animal hepatocytes and liver microsomes—prediction of metabolism<i>in vivo</i>

Lacarelle, Bruno; Marre, F; Durand, Alain; Davi, H.; Rahmani, Roger

doi:10.3109/00498259109039472

Cited by 16 publications

(2 citation statements)

References 12 publications

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“…However, the major drawback of this model is the interspecics variability of drug metabolism at the hepatic level, leading to a hazard ous extrapolation to man of results obtained with animal hepatocytes [ 15,16]. In ourstudy, much more acitretin was transformed into etretinate by monkey hcpatocytes than cells of other species.…”

Section: Discussionmentioning

confidence: 99%

Acitretin Biotransformation into Etretinate: Role of Ethanol on in vitro Hepatic Metabolism

Laugier¹,

Sousa

Bun³

et al. 1994

Dermatology

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The aim of this study was to investigate the possible esterification of acitretin into etretinate by using hepatocytes in primary culture from the rat, monkey, dog and man. With rat and human hepatocytes, etretinate was detectable only when ethanol was co-administered with acitretin. With monkey and dog cells, traces of etretinate were found without ethanol addition, but the esterification of acitretin was highly enhanced by ethanol. The metabolic profile was not changed when cells were pre-incubated with ethanol. Therefore acitretin seems to act rather as a substrate than an enzymatic inducer.

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Section: Discussionmentioning

confidence: 99%

Acitretin Biotransformation into Etretinate: Role of Ethanol on in vitro Hepatic Metabolism

Laugier¹,

Sousa

Bun³

et al. 1994

Dermatology

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“…Furthermore, it appears to improve performance in behavioural tasks involving learning and memory [16][17][18][19]. Pharmacokinetic and pharmacodynamic investigations have been performed in vitro as well as in animals and humans [20][21][22][23]. In humans, minaprine was initially used in France for the treatment of several psychological 'inhibitory-state' syn dromes, defined as decreased spontaneous activity, re duction in basic drives, slowed thoughts, memory impair ment, feelings of tiredness and social withdrawal [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Multicentric Double-Blind Study Comparing Efficacy and Safety of Minaprine and Imipramine in Dysthymic Disorders

Salzmann

Robin

1995

Neuropsychobiology

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This multicentre study compares the therapeutic efficacy and safety of minaprine (200 mg) to that of imipramine (50, 75, 100 mg) in the treatment of patients over 40 years suffering from dysthymic disorders as diagnosed according to DSM III. After 4–7 days on placebo, 67 patients were randomly assigned to receive either drug for a period of 6 weeks in a double-blind manner. As rated by the Hamilton Depression Rating Scale and evaluated by exploratory statistics, minaprine showed similar efficacy to imipramine in these patients. Minaprine was better tolerated than imipramine according to the physicians’ tolerance rating (p < 0.05) and produced significantly fewer symptoms of the autonomic nervous system as compared to imipramine (p < 0.01).

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Relationships betweenin vitro andin vivo biotransformation of drugs in humans and animals: pharmaco-toxicological consequences

et al. 1995

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Given the crucial role played by hepatocytes in the detoxification/toxification processes of drugs, these cells have been increasingly used during the last decade in various pharmaco-toxicological areas. The majority of these studies have, however, dealt with animal cells, although examples of failures in the extrapolation of the data to man are frequent. This drawback, together with the ethical considerations in performing in vivo experiments, makes the application of the human hepatocyte model critical in the preclinical evaluation of new compounds. However, before making extensive use of these promising tools for prospective pharmaceutical research, one must ensure that they can generate data that correlate well with those obtained in vivo. This is only possible through extensive studies on drugs showing a variety of phase I and phase II metabolic pathways in hepatocytes from different species, including man, and comparison with in vivo data. Providing this validation step is undertaken, the use of such systems in drug research and development may greatly enhance the rational design of safe and effective drugs, allowing savings in time, cost and test materials as well as minimizing the use of animals.

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Metabolism of minaprine in human and animal hepatocytes and liver microsomes—prediction of metabolismin vivo

Cited by 16 publications

References 12 publications

Acitretin Biotransformation into Etretinate: Role of Ethanol on in vitro Hepatic Metabolism

Acitretin Biotransformation into Etretinate: Role of Ethanol on in vitro Hepatic Metabolism

Multicentric Double-Blind Study Comparing Efficacy and Safety of Minaprine and Imipramine in Dysthymic Disorders

Relationships betweenin vitro andin vivo biotransformation of drugs in humans and animals: pharmaco-toxicological consequences

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