Pharmacokinetics in immature animals: a review

Nouws, J. F. M.

doi:10.2527/1992.70113627x

Cited by 38 publications

(39 citation statements)

References 22 publications

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“…As the animal grows up, the ability to metabolize xenobiotics becomes greater, reaching the adult level in a variable period depending on the enzyme and the species involved [18,22], However, this rule has ex ceptions. Some enzymes have been reported to have an ontogenic development similar to that described in the present report.…”

Section: Resultsmentioning

confidence: 99%

“…Although most of the enzymes responsible for the metabolic degradation of drugs are present at birth, their activity usually is con siderably lower in neonates than in adults [ 18,19], A great number of drugs are eliminated from the body by metabolic pathways involv ing the CYP superfamily of enzymes, most of which are not expressed at the adult level throughout the early postnatal period [11,20,21], This fact, besides the reported enhanced perinatal sensitivity to some drugs, has created a cautious attitude towards drug use during the perinatal period, gestation and lac tation. As the animal grows up, the ability to metabolize xenobiotics becomes greater, reaching the adult level in a variable period depending on the enzyme and the species involved [18,22], However, this rule has ex ceptions.…”

Section: Resultsmentioning

confidence: 99%

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Enhanced Diltiazem Deacetylase Activity in Pre-Term and Full-Term Rabbits Compared with Adult Rabbits

et al. 1997

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The in vitro metabolic activity of the esterase responsible for the hydrolysis of diltiazem (DTZ) to its deacetylated metabolite (Ml) was determined in an age-dependent fashion using the rabbit as an animal model. The presence of the enzyme in several tissues (liver, lung, small ntestine, and brain) and in whole blood from pre-term and full-term fetuses, full-term newborns, yound and adult rabbits was examined. To this end, DTZ was spiked to 10000-g tissue homogenates and whole blood to yield a final concentration of 1 μg/ml. Serial samples were withdrawn from the incubation medium up to 240 min and assayed for DTZ and M1 concentration. In all tissues examined there was a net production of M1. Chemical breakdown and stability studies confirmed the metabolic origin of the Ml formed throughout the incubation. In pre-term fetuses (25 days of gestation) the brain was found to be the most active tissue in eliminating DTZ (brain > liver > lung > small intestine). This trend changed in young and adult rabbits (lung = brain > liver > small intestine). Although an important age-dependent DTZ deacetylase activity was observed in blood, it was not included in the comparison between organs because of the unequal composition of the incubation medium. In conclusion, results showed that fetuses and newborn rabbits have a similar, and in some instances higher, DTZ deacetylase activity to that in adults (p < 0.05). In vitro findings were further confirmed by in vivo experiments.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Enhanced Diltiazem Deacetylase Activity in Pre-Term and Full-Term Rabbits Compared with Adult Rabbits

et al. 1997

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“…The difference with the present experiment may be age-related because young pigs were used by Kokue et al (1994). Indeed, it has been shown that intestinal mucosa may be more permeable in young pigs than in adults to oral administration of polar antibiotics (Nouws 1992). It has been proposed that animals can absorb FA and utilize it after converting to a reduced form at the site of intestinal absorption and in the liver.…”

Section: Discussionmentioning

confidence: 65%

Effect of oral administration of folate sources on plasma folate levels in pigs: Comparison between reduced and oxidized forms of folate

Mizuno¹,

Kokue²,

Ohnishi³

et al. 1997

Can. J. Anim. Sci.

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. Effect of oral administration of folate sources on plasma folate levels in pigs: Comparison between reduced and oxidized forms of folate. Can. J. Anim. Sci. 77: [497][498][499][500][501][502]. Two experiments were conducted to evaluate the response of plasma folate levels after oral administration of oxidized or reduced forms of folates, using seven Göttingen minipigs. Plasma folate levels, tetrahydrofolate (THF) and 5-methyltetrahydrofolate (5CH 3 -THF), were determined by high-performance liquid chromatography with electrochemical detection. In exp. 1, the absorption of the oxidized form of folate [(synthetic folic acid(FA)] and the reduced forms of folate (5-formyltetrahydrofolate (5HCO-THF), liver powder and digested bacterial cell powder (DBCP) were evaluated by measuring changes in plasma folate levels after a single oral administration. Liver powder and DBCP contained much reduced forms of folate. The administration of the reduced form of folates increased plasma THF levels while the levels of plasma THF and 5CH 3 -THF decreased after FA administration. In exp. 2, plasma folate levels were measured after long-term oral administration of FA for 30 d. Immediately after the beginning of the administration, the levels of both THF and 5CH 3 -THF decreased significantly and remained at a low level during the 30-d administration. Supplementation of sow feed with FA has been recommended in many countries improving reproductive performance. The present study, however, suggests that the oral administration of an oxidized form of folate, FA, may not be as effective as previously thought, and the reduced forms of folate might be preferable for the supplementation of pig feeds. Sci. 77: 497-502. Deux expériences avaient pour objet d'évaluer la réponse des concentrations plasmatiques de folates à l'administration orale à des porcs miniatures Göttingen de folate dans la forme réduite ou dans la forme oxydée. Les concentrations plasmatiques des folates, tétrahydrofolate (THF) et méthyle-5 tétrahydrofolate (CH 3 -5THF) étaient mesurées par HPLC à détection électrochimique. Dans la première expérience l'absorption d'une forme oxydée (acide folique de synthèse AF) et d'une forme réduite formyl-5 tétrahydrofolate (HCO-5THF) ainsi que de poudre de foie et de poudre de digesta de cellules bactériennes (PDCB) était comparée quant à l'effet sur les modifications des taux plasmatiques de folate après une seule administration orale. La poudre de foie et la PDCB contenaient beaucoup de folate sous la forme réduite. L'administration de folate réduit donnait lieu à un accroissement des taux plasmatiques de THF, tandis que celle de la forme oxydée (AF) abaissait les concentrations de THF et de CH 3 -5THF. Dans la deuxième expérience, les niveaux plasmatiques de folate étaient mesurés après des administrations journalières de AF répétées pendant 30 jours. Dès le début, on observait une chute significative des concentrations de THF et de CH 3 -5THF qui se maintenaient ensuite à ces niveaux tout au long de l'expérience. Beaucoup de pay...

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“…The high concentrations of roscovitine found in pup brain tissue indicate that roscovitine passes freely through the blood brain barrier (BBB). This difference in roscovitine kinetics might be due to the immaturity of the CYP450 enzymes responsible for roscovitine metabolism [149] or to the immaturity of the BBB. Roscovitine is metabolized mainly by the CYP3A4 and CYP2B6 enzymes in human [139].…”

Section: Age-dependent Kinetics and Pharmacodynamics Of Roscovitine Imentioning

confidence: 99%

From Roscovitine to CYC202 to Seliciclib – from bench to bedside: discovery and development

Zhelev

Trifonov²,

Wang³

et al. 2013

Biodiscovery

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This monograph reviews the discovery and development of the cyclindependent kinase inhibitor roscovitine (R-roscovitine, CYC202, Seliciclib). The authors summarise the in vitro and in vivo data that have formed the basis for clinical investigation of Seliciclib as an anti-cancer drug. Kinase selectivity, cellular effects and the pharmacological properties of the drug are discussed in addition to the clinical results of Seliciclib being reviewed. Novel results on the effect of the drug in cardiac hypertrophy are summarized and potential applications of Seliciclib in other therapeutic areas, including, inflammation, virology, glomerulonephritis and polycystic kidney disease, are discussed. Finally the authors argue that optimisation of the therapeutic effect of kinase inhibitors such as Seliciclib can be enhanced using a systems biology approach involving mathematical modelling of the molecular pathways regulating cell growth and division. Seliciclib -discovery and developmentBioDiscovery 2 December 2013 | Issue 10 | 1

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Pharmacokinetics in immature animals: a review

Cited by 38 publications

References 22 publications

Enhanced Diltiazem Deacetylase Activity in Pre-Term and Full-Term Rabbits Compared with Adult Rabbits

Enhanced Diltiazem Deacetylase Activity in Pre-Term and Full-Term Rabbits Compared with Adult Rabbits

Effect of oral administration of folate sources on plasma folate levels in pigs: Comparison between reduced and oxidized forms of folate

From Roscovitine to CYC202 to Seliciclib – from bench to bedside: discovery and development

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