Developing Advanced Patient-Specific In Silico Models: A New Era in Biomechanical Analysis of Tooth Autotransplantation.

Introduction: As personalized medicine advances, there is an escalating need for sophisticated tools to understand complex biomechanical phenomena in clinical research. Recognizing a significant gap, this study pioneers the development of patient-specific in silico models for tooth autotransplantation (TAT), setting a new standard for predictive accuracy and reliability in evaluating TAT outcomes.

Methods: Development of the models relied on 6 consecutive cases of young patients (mean age 11.

Liarozole fumarate inhibits the metabolism of 4-keto-all-trans-retinoic acid.

The metabolism of 4-keto-all-trans-retinoic-acid (4-keto-RA), a biologically active oxygenated metabolite of all-trans-retinoic (RA), has been examined. In vitro, incubation of [14C]4-keto-RA with hamster liver microsomes in the presence of NADPH produced two major radioactive metabolites which were more polar than the parent compound. Following isolation, appropriate derivatization and analysis by GC-MS, these compounds were tentatively identified as 2-hydroxy- and 3-hydroxy-4-ketoretinoic acid.

The metabolism and excretion of risperidone after oral administration in rats and dogs.

The metabolism and excretion of risperidone (RIS; 3-[2-[4-(6-fluoro-1,2-benzisoxazole-3-yl)-1-piperidinyl]ethyl]-6,7,8,9- tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one), a novel antipsychotic drug, were studied after single po administration of radiolabeled RIS to rats and dogs. In rats, the excretion of the radioactivity was very rapid. The predominant excretion in rat feces (78-82% of the dose) was related to an extensive biliary excretion of metabolites (72-79% of the dose), only a small part of which underwent enterohepatic circulation.

Comparative metabolism of flunarizine in rats, dogs and man: an in vitro study with subcellular liver fractions and isolated hepatocytes.

1. The biotransformation of 3H-flunarizine ((E)-1-[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine dihydrochloride, FLUN) was studied in subcellular liver fractions (microsomes and 12,000 g fraction) and in suspensions or primary cell cultures of isolated hepatocytes of rats, dogs and man. The major in vitro metabolites were characterized by h.

Suggested mechanism for the formation of 15-hydroxyeicosatrienoic acid by rat epidermal microsomes.

We have previously demonstrated that rat epidermal microsomes NADPH-dependently convert 15(S)-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) into 15-hydroxy-5,8,11-eicosatrienoic acid (15-HETrE). The present study examines the mechanism of this reductive conversion. Rat epidermal microsomes were incubated with [1-14C]15-HPETE in the presence and absence of NADPH.

NADPH-dependent formation of 15- and 12-hydroxyeicosatrienoic acid from arachidonic acid by rat epidermal microsomes.

Rat epidermal microsomes were incubated with [1-14C]-arachidonic acid for 30 min at 37 degrees C in the absence and presence of NADPH. The arachidonate metabolites that eluted in the "monohydroxy acid fraction" on reverse-phase high performance liquid chromatography (HPLC) were methylated, purified by straight-phase HPLC and analyzed by chromatography with standard compounds, UV spectroscopy and/or gas chromatography-mass spectrometry (GC-MS). In the absence of NADPH, epidermal microsomes converted arachidonic acid to two major products identified as 15(S)-hydroxy-5,8,11,13-eicosatetraenoic acid (15(S)-HETE) and 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE).

R 76713 and enantiomers: selective, nonsteroidal inhibitors of the cytochrome P450-dependent oestrogen synthesis.

The triazole derivative, R 76713 and its enantiomers R 83839(-) and R 83842(+) are effective inhibitors of the aromatization of androstenedione. For human placental microsomes, the (+) enantiomer (R 83824) is about 1.9- and 32-times more active than the racemate (IC50 2.

Biotransformation of sufentanil in liver microsomes of rats, dogs, and humans.

The biotransformation of sufentanil (SUF), an analog of the synthetic opioids fentanyl and alfentanil, was investigated in liver microsomes of rats, dogs, and humans. The drug was extensively metabolized and the metabolism was found to be very similar, both kinetically and metabolically, in the three species. The initial metabolism of SUF occurred monophasically in man and dog and biphasically in the rat over a concentration range of 0.

On the use of laser microprobe mass spectrometry for the analysis of organic biomolecules.

Laser microprobe mass spectrometry has been applied to a variety of organic polyfunctional molecules, covering a wide range of polarity and mass spectrometric behaviour. The technique apparently combines desorption under relatively soft conditions with extensive fragmentation and hence allows much structural information from intactly released thermolabiles to be obtained. The mass spectra appear unfamiliar in comparison to conventional techniques.

Perturbation of sterol biosynthesis by itraconazole and ketoconazole in Leishmania mexicana mexicana infected macrophages.

The azole antifungals ketoconazole and itraconazole possess in vitro antileishmanial activity against Leishmania mexicana mexicana amastigotes in macrophages (cell line J774G8). As in yeast and fungi, the activity is likely to be due to inhibition of the cytochrome P-450-dependent 14 alpha-demethylation of lanosterol and/or 24,25-dihydrolanosterol. Indeed, 50% inhibition of ergosterol synthesis was observed at 0.

Structural characterization of drugs and oxygenated metabolites by laser microprobe mass spectrometry (LAMMA).

Laser microprobe mass analysis (LAMMA) was used for the structural characterization of polyfunctional drugs and their oxygenated metabolites, in particular the N-oxides. The spectra usually yield the molecular weight as well as intense fragments. The structural information is characteristically distributed between the positive and negative ions.

Is the metabolism of alfentanil subject to debrisoquine polymorphism? A study using human liver microsomes.

The present study was designed to investigate whether the metabolism of the opiate analgesic alfentanil in humans is subject to the debrisoquine 4-hydroxylation polymorphism. The role of a specific cytochrome P-450 form, debrisoquine 4-hydroxylase, in the metabolism of alfentanil was investigated by competitive inhibition experiments over the concentration range 4-100 microM. Alfentanil was incubated with human liver microsomes in the presence of an NADPH-generating system.

Alfentanil pharmacokinetics and metabolism in humans.

The metabolism of alfentanil was studied in three healthy subjects after a 1-h infusion of 2.5 mg alfentanil-3H. One of the subjects was a poor hydroxylator of debrisoquine.

Absorption, metabolism and excretion of ketanserin in man after oral administration.

The absorption, metabolism and excretion of ketanserin [+)-3-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-2,4(1H,3H)- quinazolinedione, R 41 468), a novel serotonin S2-receptor antagonist used in hypertension, was studied after a single oral dose of 14C-ketanserin tartrate in three healthy subjects. Absorption from the gastrointestinal tract was rapid and almost complete. The excretion of radioactivity amounted to about 90% after 4 days and was more abundant in urine (68%) than in faeces (24%).

Ketoconazole inhibits the in vitro and in vivo metabolism of all-trans-retinoic acid.

Ketoconazole, an antifungal agent and inhibitor of certain mammalian cytochrome P-450-dependent enzymes, was studied for its effects on the in vitro and in vivo metabolism of all-trans-retinoic acid (RA). In vitro, ketoconazole (Ki = 0.75 microM) inhibited, in an apparently competitive manner, the cytochrome P-450-mediated metabolism to 4-hydroxy- and 4-keto-retinoic acids by hamster liver microsomes.

Excretion and biotransformation of cisapride in rats after oral administration.

The excretion and biotransformation of cisapride, a novel gastrokinetic drug, were studied after single (10, 40, and 160 mg/kg) and repeated (10 mg/kg/day) po administration to rats, using three different radiolabels. In fasted rats, cisapride was absorbed almost completely, except for the 160 mg/kg dose. Cisapride was metabolized extensively to at least 30 metabolites.

Excretion and biotransformation of cisapride in dogs and humans after oral administration.

The excretion and biotransformation of cisapride, a novel gastrokinetic drug, were studied after a single po dose of [14C]cisapride in dogs and humans. The excretion of radioactivity amounted to 97% within 4 days after a 1 mg/kg dose in dogs (72% in feces and 25% in urine). After a 10-mg dose in humans, 44% was excreted in the 0-24-hr urine and 37% in the 0-35-hr feces; excretion was complete within 4 days.

Identification of a biliary metabolite of cisapride.

Radiolabeled cisapride was administered orally to male Wistar rats. The drug was metabolized extensively, resulting in the formation of a large number of urinary and faecal metabolites. In bile-cannulated rats a major metabolite was excreted with the bile whose structure could not be elucidated with the aid of the registered electron impact and desorption chemical ionization spectra.

Metabolism of alfentanil by isolated hepatocytes of rat and dog.

1. The biotransformation of 3H-alfentanil was studied using suspension cultures of isolated hepatocytes of male and female rats and of dogs. 2.

Excretion and biotransformation of alfentanil and sufentanil in rats and dogs.

The excretion and biotransformation of alfentanil (ALF) and sufentanil (SUF), two recent analogues of the synthetic opioid fentanyl, were studied after single iv administration of the tritium-labeled drugs in male rats and dogs. The drugs were almost completely metabolized in the two species, which resulted in a large number of metabolites. The excretion of the metabolites was rapid and exceeded 95% within 4 days, except for that of ALF metabolites in dogs (about 85%).

Identification of 17 alpha,20 alpha-dihydroxyprogesterone in testicular extracts after incubation with ketoconazole.

The antifungal ketoconazole affects testosterone synthesis in dispersed rat testicular cells. In the presence of ketoconazole an accumulation of 17 alpha,20 alpha-dihydroxyprogesterone has been observed. This steroid was isolated from the testis of Wistar rats after a [4-14C]progesterone incorporation in the presence of ketoconazole.

Excretion and biotransformation of ketanserin after oral and intravenous administration in rats and dogs.

The excretion and biotransformation of ketanserin, a novel serotonin S2-receptor blocking agent used in hypertension and related diseases, were studied after single po (1 or 10 mg/kg) and iv (2.5 mg/kg) administration in rats and dogs, using two different radiolabels. Orally administered ketanserin was well absorbed and almost completely metabolized in both species.

Plasma levels, biotransformation and excretion of oxatomide (R 35 443) in rats, dogs and man.

Plasma levels, biotransformation and excretion of oxatomide were studied after single oral doses of 14C-oxatomide in male rats, dogs and humans. Oxatomide was very well absorbed, and almost completely metabolized in the three species. Excretion of the metabolites was very rapid and complete within a few days; the 14C label was excreted more in the faeces (54-62%) than in the urine (27-40%).