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PubMedDate not supplied

Pharmacokinetic profile of metaclazepam (Talis), a new 1.4-benzodiazepine. Influence of different dosage regimens on the pharmacokinetic profile of metaclazepam and its main metabolite under steady-state conditions.

The pharmacokinetic parameters of the new 1.4-benzodiazepine metaclazepam (Talis) were investigated. In particular, the question of whether the drug and/or its main metabolite accumulates in the body under steady-state conditions was studied. Two dosage regimens were compared by a randomized two-way crossover design: a once-a-day dosing (15 mg metaclazepam in the evening, = A) versus a twice-a-day dosing (5 mg in the morning plus 10 mg in the evening, = B) over ten days in twelve healthy male volunteers. Plasma levels of metaclazepam and its major biotransformation product, N-desmethylmetaclazepam, were determined. Comparing the treatments, significant differences were found for Cmax, but not for AUC-3 and Tmax. These results are also valid for the comparison of days 1 and 10 of each treatment. Higher Cmax values for dosage regimen A were found but Tmax and Cl/F remained stable in both treatments taking into account that 12 hours after the first medication, another dosing took place in treatment B. Eight hours after application, plasma levels were markedly low, Cmax values after single-dosing were nearly twice as high as after multiple dosing. Therefore based on these pharmacokinetic findings, a second dosing seems to be necessary; the clinical relevance needs further investigation. It has been reported, in fact, that it is in general very difficult to demonstrate a correlation between blood levels and therapeutic effects for 1.4-benzodiazepines (1,2).

Adult↗
PubMed1986

Ecotoxicological profile of xylenes. Working Party on Ecotoxicological Profiles of Chemicals.

The xylenes (o, m, p), which are produced in large amounts and widely used, must be considered as environmental contaminants, as they have been identified in the atmosphere of many countries. Their acute and chronic toxicity in mammals is moderate. Mutagenic and teratogenic properties can be excluded. Carcinogenic potential has been at present inadequately studied. In man some disturbances are evident at the concentration of 45 ppm. Hepatic metabolism is a valid process of detoxification and its high rate limits the risk of accumulation of the xylenes in adipose tissue. Ecotoxicological data refer almost exclusively to water. No long-term tests have been made. However, the high volatility, elevated elimination, and the low factor of accumulation suggest the impact on aquatic environment should be limited. Xylenes are easily biodegraded by many microorganisms. Photoxydation is one of the main degradation processes, responsible for the disappearance of the xylenes from the atmosphere.

Animals↗
PubMed2006

Quantification of mentolabial profile using lateral roentgen cephalography and profile reconstruction by mandibular osteotomy in healthy adults and patients with scar contracture following severe facial burns.

Here mentolabial form including lateral facial contour and bony contour in healthy adults was studied to refer to values of normal mentolabial form using lateral roentgen cephalography. In soft tissue of healthy adults, thickness of mentolabial soft tissue was greater for men than for women. Degree of mentolabial curvature was greater for men than for women. In severe facial burn patients, the micrognathia-like deformity was evaluated compared with the reference values. In soft tissue of severe facial burn patients, loss of mentolabial sulcus and eversion of the lower lip were characteristically analyzed, suspecting that the major cause was scar contracture. These statistical data contribute to reconstruction of micrognathia-like deformity after severe facial burn to lead to favorable mentolabial form. It is shown that osteotomized genio-advancement produced ideal mentolabial form in severe facial burn patients, who had not been satisfied with the form by conventional operative methods, free skin flap, skin flap or free skin graft. And that the analyzed data, especially in the parameter of thickness of mentolabial sulcus, was improved.

Adolescent↗
PubMed2004

Atypical antipsychotics: matching receptor profile to individual patient's clinical profile.

Understanding common pharmacologic and clinical "class" actions associated with atypical antipsychotics certainly reveals how these agents are alike, but what about unique differences from one agent to another? Atypical antipsychotics are also a heterogeneous group of agents that have complex pharmacologic entities, acting upon multiple dopamine receptors (D2, D1, D3, and D4) and multiple serotonin receptors (5-HT2A, 5-HT2C, 5-HT1A, and 5-HT1D, among others). Atypical antipsychotics also interact with noradrenergic (alpha 1- and alpha 2-adrenergic receptor blockade), histaminergic (H1-receptor blockade), and cholinergic (muscarinic M1 blockade) neurotransmitter systems as well as with monoamine (D, 5-HT, and norepinephrine reuptake blockade) transporters. However, no two atypical antipsychotics possess the same portfolio of actions upon all of these additional neurotransmitter systems.

Adult↗
PubMed1992

[Profile of pO2. I. Profile of transretinal pO2 in hypoxia].

Transretinal PO2 measurements during systemic hypoxia, made during variations of the PO2 by steps of 10 mmHg between 120 and 30 mmHg, have shown that the PO2 values measured at the inner-retina up to half the thickness of the retina remained stable. On the other hand, those measured at the choroid and at the outer-retina decreased in a linear manner according to the variations of PaO2. These results suggest a regulation in the retinal blood flow, allowing the PO2 to remain stable for the different steps of hypoxia studied. On the other hand, the values measured at the choroid and at the outer-retina showed the absence of regulation in the choroidal blood flow during hypoxia. Systemic hypoxia may affect the metabolism of the photoreceptors and the pigmentary epithelium.

Animals↗
PubMed2002

Neuropsychological profiles delineate distinct profiles of schizophrenia, an interaction between memory and executive function, and uneven distribution of clinical subtypes.

Neuropsychological performance in 151 patients with schizophrenia was examined using cluster analysis to identify neurocognitive subtypes. Hierarchical and iterative partitioning methods identified four clusters using an extended neuropsychological battery. Consistent with previous findings two extreme clusters were characterized by near normative performance and profound global dysfunction, respectively. The two remaining neurocognitive clusters displayed moderate-severe dysfunction and were differentiated by unique patterns of abstraction and flexibility, attention, spatial memory, and sensory-perception. Analysis of variance revealed an interaction between global memory and executive function for clusters III and IV. Although limited cluster differences were found relative to clinical and historical data, the distribution of previously defined clinical subtypes was uneven among neurocognitive clusters. Paranoid patients were significantly more likely to be classified into cluster II and disproportionately absent from clusters I and IV. Patients with negative and disorganized clinical subtypes comprised a disproportionate component of clusters I and IV but were less likely to be classified in cluster II. This suggests greater correspondence than previously postulated between systems responsible for clinical symptomatology and those moderating neurocognitive dysfunction.

Adult↗
PubMed2004

Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles?

Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c), as well as the TC:HDL-c ratio, were compared in patients receiving different antiretroviral therapy regimens. Patients receiving first-line regimens including protease inhibitors (PIs) had higher TC and TG levels and TC : HDL-c ratios than did antiretroviral-naive patients; patients receiving 2 PIs had higher levels of each lipid. Ritonavir-containing regimens were associated with higher TC and TG levels and TC : HDL-c ratios than were indinavir-containing regimens; however, receipt of nelfinavir was associated with reduced risk of lower HDL-c levels, and receipt of saquinavir was associated with lower TC : HDL-c ratios. Patients receiving nonnucleoside reverse-transcriptase inhibitors had higher levels of TC and LDL-c than did antiretroviral-naive patients, although the risk of having lower HDL-c levels was lower than that in patients receiving a single PI. Efavirenz was associated with higher levels of TC and TG than was nevirapine.

Adult↗