Biotransformation of Drugs and other Xenobiotics during Postnatal development

Klinger, W

doi:10.1016/s0940-2993(96)80104-7

Cited by 18 publications

(28 citation statements)

References 918 publications

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“…Reviews on concepts and therories of development and aging have been published by several authors respectively editors (cp. Klinger, 1996). But there is no convincing concept or proof on the molecular-biological basis of an internal clock which regulates and controls individual development, aging and death.…”

Section: Discussionmentioning

confidence: 99%

“…Condensing our own extensive reviews (Klinger 1982(Klinger , 1987(Klinger , 1996 and those of others (cp. Klinger 1996) a summary of the main findings can be given.…”

Section: General Developmental Aspects Of Biotransformation Of Drugs mentioning

confidence: 99%

“…In the rat, liver mass has the highest percentage of whole body mass in 30-to 60-day-old animals. Liver growth is stimulated by the beginning of food uptake after the 15th day of life (David 1985, Klinger 1996.…”

Section: Morphological Basismentioning

confidence: 99%

“…Microsomal glucose-6-phosphate dehydrogenase activity for the NAD H2 and NADPH 2 regenerating systems is low in rat hepatocytes at an age of 2 weeks, then an increase can be observed after weaning, more dramatically after 8 weeks of age, maximal values could be detected at an age of 12 -16 weeks (cp. Klinger 1996).…”

Section: Biochemical Basismentioning

confidence: 99%

“…All reaction types of phase I and phase II need individual investigation in different organs and tissues, respectively, and in various laboratory animals (cp. Klinger 1996).…”

Section: Phase II Reactionsmentioning

confidence: 99%

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Developmental pharmacology and toxicology: Biotransformation of drugs and other xenobiotics during postnatal development

Klinger

2005

Eur. J. Drug Metab. Pharmacokinet.

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The following conclusions can be drawn: Depending on reaction type, species (strain), organ (tissue) and sex (in rats and mice) both phase I and phase II ractions show developmental patterns with maximum activities in juvenile or young adult animals. In man drug disposition in newborns is also generally much lower than in children and young adults. Mammals with long gestation periods are born with considerable activities and adult values are reached earlier than in animals with short gestation periods. Highest activities (with very few exceptions) are observed in liver postnatally. With increasing age, in all laboratory animals and in man, a decline of biotransformation capacity is observed. Most of these reactions are inducible by inducers of the phenobarbital-, 3-methylcholanthrene- and tetrachlorodibenzo-p-dioxine-, steroid- or alcohol-type. Inducibility also depends on reaction type, species (strain), organ (tissue) and sex (in rats and mice). Inducibility begins in the earliest embryonic stage and reaches high rates in species with long gestation periods before birth, and at or after birth in species with short gestation periods. The beginning of high inducibility depends also on inducer types and the induced parameter. Inducible reactions can be increased in immature as well as in very old animals up to or above the level of adult animals. Isozymes may show different developmental patterns and inducibilities. Development and induction of isozymes catalyzing different reactions can be triggered in clusters. There is increasing evidence that basic biotransformation activities as well as their inducibilities by foreign compounds are essentially influenced by a kind of temporal genetic control during the whole life span. When we compared different monooxygenase reactions and their inducibility (Klinger et al., 1968) both the presence of P450 isozymes and their different inducibility as well as their different developmental pattern became evident, the direct proof of which was given 10 years later by the Nebert group (Atlas et al. 1977). Functional heterogeneity was demonstrated by differential development and inducibility by glucocorticoids also for UDP-glucuronosyl transferase (Wishart, 1978): in the rat the increased fetal glucocorticoid activity between days 17 and 20 of gestation triggers the surge to adult or higher than adult activities. This cluster of the so-called late fetal glucuronyltransferase group is distinctly different from the neonatal or postnatal cluster with peak values after birth and a pronounced inducibility by 3-methylcholanthrene, but not by steroids. These different transferase clusters can be differentiated by different substrates, too. To get an overview on the postnatal development of the most important phase I and phase II reactions and also for the heme biosynthetic pathway as a prerequisite for the P450 synthesis, a compilation of literature data similar to a score was constructed with the aim to recognize parallel developments, possible common control and regulation mechanisms, ...

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Section: Discussionmentioning

confidence: 99%

“…Condensing our own extensive reviews (Klinger 1982(Klinger , 1987(Klinger , 1996 and those of others (cp. Klinger 1996) a summary of the main findings can be given.…”

Section: General Developmental Aspects Of Biotransformation Of Drugs mentioning

confidence: 99%

Section: Morphological Basismentioning

confidence: 99%

Section: Biochemical Basismentioning

confidence: 99%

“…All reaction types of phase I and phase II need individual investigation in different organs and tissues, respectively, and in various laboratory animals (cp. Klinger 1996).…”

Section: Phase II Reactionsmentioning

confidence: 99%

See 3 more Smart Citations

Developmental pharmacology and toxicology: Biotransformation of drugs and other xenobiotics during postnatal development

Klinger

2005

Eur. J. Drug Metab. Pharmacokinet.

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Efforts to establish an animal model of Fanconi syndrome after ifosfamide administration to rats

Appenroth

Werner

Lupp

et al. 2007

J of Applied Toxicology

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About 10% of children develop Fanconi syndrome (FS) a few months after ifosfamide (IFO) treatment. To establish an animal model, IFO was injected as 4 or 5 treatment courses (TCs, once daily for 3 consecutive days), to adult female rats (AF, 8 mg 100 g(-1) body wt, 4 TCs), to young female rats (YF, 8 mg 100 g(-1) body wt, 5 TCs) and to male rats (M, 6 mg 100 g(-1) body wt, 4 TCs). In the adult female rats, polyuria with electrolyte and albumin wasting occurred acutely, 2 days after the first treatment course. After the third treatment course, 30% of the rats died, but survivors showed a reduced excretion of electrolytes and glucose. The body weight increase was significantly diminished in adult female and male rats by about 25% or 70%, respectively. Up to 5 months after 5 TCs in young female rats, 15% of the animals died but the survivors did not show any sign of renal failure. In males, 28% of the rats died and in surviving animals the excretion of electrolytes, proteins and glucose as well as GFR were reduced 7 weeks after the last treatment course. There were no pathomorphological changes in kidney and liver. Determination of renal and hepatic cytochrome P450 activities indicated that results of adult female and male rats could be caused by starving, known as a common side effect of IFO, and not by its nephrotoxicity. Altogether, it was not possible to establish a model of a Fanconi syndrome persisting after cessation of IFO treatment in our rat strain, whereas acute, FS-like IFO effects on the kidney could be shown.

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Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport

Petzinger¹

1994

Reviews of Physiology, Biochemistry and Pharmacology

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Biotransformation of Drugs and other Xenobiotics during Postnatal development

Cited by 18 publications

References 918 publications

Developmental pharmacology and toxicology: Biotransformation of drugs and other xenobiotics during postnatal development

Developmental pharmacology and toxicology: Biotransformation of drugs and other xenobiotics during postnatal development

Efforts to establish an animal model of Fanconi syndrome after ifosfamide administration to rats

Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport

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