RESUMO
Objective: To analyze the age distribution characteristics of different cancers in the world according to the database from Cancer Incidence in Five Continents published by the International Association of Cancer Registries, and to compare the age differences of cancer incidence in different regions. Methods: Cancer incidence data from volume XI of Cancer Incidence in Five Continents including 339 population-based cancer registries in 65 countries during 2008-2012 have been extracted. The average age of cancer incidence in different regions, gender and cancer sites were analyzed and stratified according to the human development Index and the level of national or regional development UN Development. The Segi's world standard population (world standard) was standardized to calculate the average age of the cancer incidence and to analyze the effect of age structure of the population on the average age of cancer diagnosis. Results: This study included 4 812 008 148 person-years in the global population (including 2 367 458 302 men and 2 444 549 846 women), and 21 892 093 of the new cancer cases, including 11 450 515 men and 10 441 578 women. The analysis showed that the average age of cancer incidence in the world was 65.73 years, and men and women were 66.70 and 64.67 years old, respectively. Among them, the average incidence age of testicular cancer was the youngest, with an average age of 36.67 years, and that of gallbladder cancer was the highest with average age of 71.55 years. After adjusting for population structure, the average incidence age was highest in gallbladder cancer, followed with bladder cancer and prostate cancer, and the testicular was with the lowest average age of incidence, followed by bone cancer and brain tumor. The results showed that the average age of cancer incidence in developed countries or regions was 66.38 years old, and that in less developed countries or regions was 61.75 years old, but in China it was 63.47 years old. According to the human development index (HDI), the higher the country or region with HDI, the higher the average age of cancer incidence, and the difference is reduced after the adjustment of the age structure of the population. Conclusions: There are different characteristics of the age distribution for different cancer sites. In terms of the age of cancer incidence, those of gallbladder cancer and bladder cancer are relatively old, while those of the testis, bone and thyroid cancer are relatively young. The average age of cancer incidence in China is between developed and less developed countries. Prevention and control of cancer should be carried out according to the age distribution characteristics of different cancers.
Assuntos
Distribuição por Idade , Saúde Global/estatística & dados numéricos , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Adulto , Idoso , China , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Sistema de Registros , Distribuição por Sexo , Neoplasias Testiculares/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/epidemiologiaRESUMO
We have semi-synthesized 52 molecular species of saturated diacyl mixed-chain phosphatidylcholines. All 52 phosphatidylcholine molecules are highly asymmetrical with delta C/CL values in the range of 0.43-0.63. The aqueous dispersions of these phosphatidylcholines have been studied by the high-resolution differential scanning calorimetric (DSC) technique. Upon heating, the lipid dispersions prepared individually from these 52 phosphatidylcholines all exhibit a sharp, single, endothermic peak at a characteristic temperature or Tm, implying that the self-assembled lipid molecules in excess water undergo the mixed interdigitated gel to the liquid-crystalline phase transition. The Tm values obtained from aqueous lipid dispersions prepared from these mixed-chain phospholipids have been analyzed based on the molecular packing model of the mixed interdigitated bilayer, and a linear relationship between the Tm and (delta C)-1 for various phospholipids at a constant value of delta is observed. Based on these linear relationships, empirical equations are derived to predict the Tm values for highly asymmetrical mixed-chain phosphatidylcholines with delta C/CL values in the range of 0.43-0.63. The predictive power of these empirical equations is shown to be very good, since a comparison between the predicted and the experimental data indicates that the largest relative error in Kelvin is only 0.4%. A table containing 81 predicted Tm values for highly asymmetrical mixed-chain phosphatidylcholines is presented. The definitions of the various structural parameters such as delta C, CL, delta C/CL and delta are given in the text.
Assuntos
Fosfatidilcolinas/química , Varredura Diferencial de Calorimetria , Matemática , TermodinâmicaRESUMO
The highly asymmetric mixed-chain phosphatidylcholines or C(X):C(Y)PC, which can self-assemble at T < Tm into the mixed interdigitated gel-state bilayer in excess water, can be divided into two groups. Group I consists of C(X):C(Y)PC with X > Y, and Group II consists of C(X):C(Y)PC with X < Y. The main phase transition temperatures (Tm) of these C(X):C(Y)PC have been analyzed in terms of two structural parameters (delta and Nf). Specifically, these structural parameters are related to the packing geometry of the lipid's acyl chains as the lipid molecules are packed either in a mixed (delta) or a hypothetically partially (Nf) interdigitated packing motif at T < Tm. Based on 28 and 29 Tm values of Group I and II C(X):C(Y)PC, two general equations are derived, respectively, by multiple regression analyses. These equations correlate systematically the Tm values of Group I and II phosphatidylcholines with their corresponding structural parameters. Using these two derived equations, the Tm values of a total of 92 molecular species of C(X):C(Y)PC are generated, and these calculated Tm values can be considered as the reliably predicted Tm values for highly asymmetric C(X):C(Y)PC which have delta C/CL values within the range of 0.42-0.66.
Assuntos
Fosfatidilcolinas/química , Temperatura , Varredura Diferencial de Calorimetria , Bicamadas Lipídicas/química , Matemática , Conformação Molecular , Estrutura MolecularRESUMO
Aqueous dispersons of L-alpha-phosphatidylethanolamine (PE) with identical saturated acyl chains are known to exhibit gel-state metastability. It is also known that the metastability in PE becomes more pronounced with decreasing acyl chain-length. In an attempt to study the metastable phase behavior of PE, we have synthesized diundecanoylphosphatidylethanolamine (diC11PE) and examined its polymorphic phase behavior. A single endothermic transition at 38 degrees C is detected between 10 and 55 degrees C by DSC for the nonheated sample of diC11PE in excess water. An immediate second heating scan done after cooling slowly of the same sample from the liquid-crystalline state shows a smaller endothermic transition at a lower temperature, 18 degrees C. However, the high-temperature transition at 38 degrees C can be detected, if the sample which has been heated above 38 degrees C is quench cooled from the liquid-crystalline to a temperature between 18 and 38 degrees C. Furthermore, two endothermic transitions at 18 and 38 degrees C and an exothermic transition at 19 degrees C are recorded for diC11PE after quench supercooling of the sample from the liquid-crystalline state to an appropriate temperature below 10 degrees C. The gel-state metastability of diC11PE can be most appropriately explained in terms of changes in interbilayer headgroup-headgroup interactions. It is suggested that the kinetically trapped supercooled metastable state may be a multilamellar structure with melted acyl chains but with strong interbilayer headgroup-headgroup interactions.
Assuntos
Bicamadas Lipídicas/metabolismo , Fosfatidiletanolaminas/metabolismo , Calorimetria , Espectroscopia de Ressonância Magnética , TemperaturaRESUMO
The influence of acyl chain-length asymmetry on the thermodynamic parameters (Tm, delta H, and delta S) associated with the reversible main phase transition of aqueous dispersions prepared from saturated diacyl phosphatidylcholines was studied by high-resolution differential scanning calorimetry. Two series of saturated diacyl phosphatidylcholines, grouped according to their molecular weights of 678 and 706, with a total number of 25 molecular species were examined. The normalized acyl chain-length difference between the sn-1 and sn-2 acyl chains for a given phospholipid molecule in the gel-state bilayer is expressed quantitatively by the structural parameter delta C/CL, and the values of delta C/CL for the two series of lipids under study vary considerably from 0.04 to 0.67. When the value of delta C/CL is within the range of 0.09-0.40, it was shown that the thermodynamic parameters are, to a first approximation, a linear function of delta C/CL with a negative slope. In addition, the experimental Tm values and the predicted Tm values put forward by Huang (Biochemistry (1991) 30, 26-30) are in very good agreement. Beyond the point of delta C/CL = 0.41, the influence of acyl chain-length asymmetry on the thermodynamic parameters deviates significantly from a linear function. In fact, within the range of delta C/CL values of 0.42-0.67, the thermodynamic parameters in the Tm (or delta H) vs. delta C/CL plot were shown to be bell-shaped with the maximal Tm (or delta H) at delta C/CL = 0.57. These results are discussed in terms of changes in the acyl chain packing modes of various phosphatidylcholine molecules within the gel-state bilayer in excess water.
Assuntos
Bicamadas Lipídicas/química , Fosfatidilcolinas/química , Varredura Diferencial de Calorimetria , Conformação Molecular , Estrutura Molecular , Peso Molecular , TermodinâmicaRESUMO
In this study, we have semisynthesized the following three molecular species of mixed-chain phosphatidylethanolamine: C(22):C(12)PE, C(16):C(18:1 delta 9)PE, and C(10):C(24:1 delta 15)PE. These lipids share a common structural characteristic, that is, they all have the same total number of carbon atoms in their acyl chains. Aqueous dispersions prepared from three sets of binary lipid mixtures, C(16):C(18:1 delta 9)PE/C(22):C(12)PE, C(10):C(24:1 delta 15)PE/C(22):C(12)PE, and C(16):C(18:1 delta 9)PE/C(10):C(24:1 delta 15)PE, were studied by high-resolution differential scanning calorimetry, leading to the construction of three temperature-composition phase diagrams. A computer program developed on the basis of the thermodynamic equations for non-ideality of mixing (or Brigg-Williams approximation) was applied to fit the calorimetric data, yielding the non-ideality parameters of mixing in the gel and the liquid-crystalline bilayers (pG and pL). Based on the shapes of these phase diagrams and the values of pG and pL, it is concluded that any two of the three molecular species of phosphatidylethanolamines under study can mix nearly ideally in the bilayer plane of the liquid-crystalline bilayer. However, these binary lipid mixtures do exhibit the gel-gel phase immiscibility over an extensive compositional region in the gel-state bilayer. By comparison with experimental data obtained with binary mixtures of saturated identical-chain phospholipids, we can conclude that mixed-chain cis-monounsaturated lipid molecules and saturated lipid molecules are highly demixed in the same two-dimensional plane of the gel-state bilayer, although the bilayer thickness difference between the lipid bilayer composed of cis-monounsaturated lipids and that of saturated lipids may be only one or two C-C bond lengths at T < Tm.
Assuntos
Varredura Diferencial de Calorimetria , Fosfatidiletanolaminas/química , Fenômenos Químicos , Físico-Química , Cristalização , Bicamadas Lipídicas/química , Substâncias Macromoleculares , Software , TermodinâmicaRESUMO
High-resolution differential scanning calorimetric studies were performed to investigate the thermotropic phase behavior of 31 molecular species of phosphatidylethanolamines in excess water. Upon reheating, the aqueous dispersions of these lipids undergo the gel to liquid-crystalline phase transitions at well defined temperatures (Tm). These Tm values were shown to relate to the structural parameters of the underlying lipid molecules in a characteristic manner. Based on these observations, an interconversion of the Tm values between saturated phosphatidylethanolamines and phosphatidylcholines is established quantitatively for the first time.
Assuntos
Bicamadas Lipídicas , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Varredura Diferencial de Calorimetria , Temperatura , TermodinâmicaRESUMO
A sample of 100 consecutively admitted cases were recruited to test the hypothesis that an abnormal dexamethasone suppression test (AbDST) is associated with decreasing clinical severity during the course of hospitalization in various diagnostic categories. Serial DSTs and psychopathological ratings were done at the end of the first and the third week postadmission, and 1 week before discharge. DST was also done at 1-year follow-up after discharge. The results of this study strongly suggest that a dual mechanism is responsible for the prevalence of AbDST. One is related to the global psychopathology of a nonspecific quantitative mechanism in various diagnostic categories. The other is a specific qualitative mechanism relating to the depressive state, as reflected in the higher prevalence of AbDST and more consistent AbDST results across different study time points in melancholia, and also in higher AbDST rates in disorders with higher depressive scores.
Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Depressivo/diagnóstico , Dexametasona , Hidrocortisona/sangue , Transtornos Neuróticos/diagnóstico , Transtornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Adulto , Transtorno Bipolar/sangue , Transtorno Depressivo/sangue , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Neuróticos/sangue , Testes de Personalidade , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/sangue , Esquizofrenia/sangue , TaiwanRESUMO
To help determine whether sustained attention deficits as measured with the Continuous Performance Test (CPT) are stable vulnerability indicators of schizophrenia, we compared the CPT performance of schizophrenic patients before and after treatment with risperidone or haloperidol. In this double blind trial, 56 schizophrenic patients were randomly assigned to a 12-week regimen of either risperidone or haloperidol, after a 1-week washout period. The patients undertook two sessions of the CPT (undegraded and 25% degraded) twice, one at the end of the washout period and the other at the end of the study. Thirty-eight patients completed the study, 19 in each group. Both groups experienced significant improvements in clinical symptoms, and the risperidone group showed no change in the severity of extrapyramidal symptoms. Despite those improvements, the CPT performance indexes did not change significantly from the beginning to the end of the study. These findings indicate that sustained attention deficits might be stable vulnerability indicators of schizophrenia.
Assuntos
Antipsicóticos/uso terapêutico , Atenção/efeitos dos fármacos , Haloperidol/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Atenção/fisiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Testes NeuropsicológicosRESUMO
BACKGROUND: Haloperidol decanoate is a long-acting depot antipsychotic agent used for the treatment of schizophrenic patients. The decanoate formulation was developed to treat schizophrenics who have a history of noncompliance with oral medication. Studies of techniques to convert from oral to depot therapy have not utilized the pharmacokinetics of the decanoate formulation. This study is a prospective evaluation for converting patients from oral to depot treatment. METHOD: Twenty-one patients meeting DSM-III-R criteria for schizophrenia participated in the study. Patients were treated with oral haloperidol for 6 weeks and then were switched to decanoate. Haloperidol decanoate 100 mg was administered on a weekly basis for the first 4 weeks. Afterward, injection intervals were increased to every 2 weeks and then to every 4 weeks. Plasma haloperidol concentrations were obtained prior to the next injection and assayed by HPLC with electrochemical detection. Patients were monitored by the psychiatrists and nursing staff for symptoms of clinical deterioration. RESULTS: All patients completed the conversion trial during the first 4 weeks without any problems or adverse side effects. By the third week, mean plasma haloperidol concentrations from the decanoate injections were comparable with those of the 10-mg oral haloperidol treatment (7.95 +/- 4.94 ng/mL vs. 7.79 +/- 4.79 ng/mL). Steady-state conditions for the decanoate therapy were achieved by the fourth week. CONCLUSION: These findings suggest that schizophrenic patients can be easily converted from oral to depot therapy without problems. Further studies with haloperidol decanoate and its conversion from oral treatment utilizing plasma concentrations are needed.
Assuntos
Antipsicóticos/administração & dosagem , Haloperidol/análogos & derivados , Haloperidol/administração & dosagem , Esquizofrenia/tratamento farmacológico , Administração Oral , Adulto , Antipsicóticos/sangue , Antipsicóticos/farmacocinética , Doença Crônica , Esquema de Medicação , Feminino , Haloperidol/sangue , Haloperidol/farmacocinética , Humanos , Injeções Intramusculares , Masculino , Cooperação do Paciente , Estudos Prospectivos , Recidiva , Esquizofrenia/sangue , Resultado do TratamentoRESUMO
Plasma levels of homovanillic acid (pHVA), a metabolite of dopamine, were measured in ninety-five Chinese schizophrenic patients free of neuroleptics for at least four weeks. These patients were treated with classical antipsychotics for six weeks. Pretreatment pHVA was positively correlated with the subsequent clinical response (r = 0.408, p < 0.0001). Good responders (BPRS improvement > or = 50%, n = 47) had higher pretreatment pHVA levels than poor responders (BPRS improvement < 50%, n = 48) (15.7 +/- 8.4 ng/ml versus 9.9 +/- 3.7 ng/ml, p < 0.0001). A higher than 15 ng/ml pretreatment pHVA level was associated with a more consistent clinical response to the subsequent treatment. Using a pHVA level of 12 ng/ml as a demarcation point, 72% of patients (34 of 47) who had pHVA > or = 12 responded whereas 65% (31 of 48) who had < 12 did not respond (chi-square = 13.02, p < 0.0001). These results suggest that higher pretreatment pHVA levels may predict a better clinical response to antipsychotics. Based upon the pHVA findings, two hypothetical subtypes of schizophrenia are proposed.
Assuntos
Flupentixol/administração & dosagem , Haloperidol/administração & dosagem , Ácido Homovanílico/sangue , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adolescente , Adulto , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Flupentixol/farmacocinética , Haloperidol/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação PsiquiátricaRESUMO
1. Haloperidol and reduced haloperidol plasma levels were measured in schizophrenic patients who received both oral (10 mg, N=16 and 20 mg, N=4) and depot haloperidol treatment 2. Patients were of Asian ethnicity and were safely and effectively converted from oral to depot therapy using a loading dose regimen using a 100 mg weekly injection interval for 4 weeks, biweekly for one month and then monthly. 3. Significant correlations were found for plasma haloperidol and reduced haloperidol levels and reduced haloperidol/haloperidol ratios between oral and depot therapy in these non-smoking patients. 4. A loading dose regimen is needed due to the long elimination half-life of decanoate of 26 days otherwise steady-state condition will not occur until 34 months of therapy. 5. Patients were maintained on monthly depot treatment for 40 weeks after the loading dose regimen and only one patient relapsed during treatment despite dosage increases. 6. The formation of reduced haloperidol remained consistent for oral and depot haloperidol treatment.
Assuntos
Antipsicóticos/administração & dosagem , Haloperidol/análogos & derivados , Haloperidol/administração & dosagem , Haloperidol/metabolismo , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
1. The studies of relationships between blood levels of reduced haloperidol HL (RH) and clinical efficacy in haloperidol (HL)-treated patients have yielded variable results. On the other hand, the contribution of RH upon HL's extrapyramidal side effects (EPS) had been suggested in animal models as well as in preliminary clinical studies with limited subjects. 2. This study explored the relationships between blood drug levels and clinical effects and EPS of HL in 48 Chinese acutely exacerbated schizophrenic inpatients. After a single-blind placebo period of one week, the patients were treated with a fixed dose 10 mg of HL for two weeks. Steady-state levels of HL and RH in plasma (n = 48) and in red blood cells (RBC) (n = 37) were measured by high performance liquid chromatography. 3. The mean RH/HL ratio in RBC in the Chinese (0.55) is lower than that in non-Chinese patients as reported in the literature (> 2), so is the RH/HL ratios in plasma. 4. No significant relationship emerged between percent improvement in BPRS total score and any of drug indices (HL, RH, sum of two compounds (HL+RH), and RH/HL ratio) in plasma and in RBC. Furthermore, the responders did not differ significantly from the nonresponders in each drug index. 5. Plasma RH levels were significantly higher in 30 patients experiencing EPS compared with the other 18 patients (mean 2.14 +/- 1.71 (S.D.) ng/ml vs. 1.38 +/- 0.37 ng/ml, p < 0.05). No significant differences in other drug indices were noted between subjects with or without EPS.
Assuntos
Tratos Extrapiramidais/efeitos dos fármacos , Haloperidol/efeitos adversos , Haloperidol/sangue , Haloperidol/farmacologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
1. Plasma haloperidol and reduced haloperidol concentration were measured in four ethnic populations. 2. Plasma samples were obtained under steady-state conditions and obtained 10-12 hours post bedtime dose and prior to the morning dose. 3. Haloperidol and reduced haloperidol plasma levels were assayed by radioimmunoassay and liquid chromatography. 4. A wide interpatient variability between haloperidol dose and plasma concentration was observed for each ethnic group. 5. The Chinese group differed from the other ethnic populations. 6. A nonlinear relationship was observed between haloperidol and reduced haloperidol plasma levels in each ethnic group. Further, the relationship of haloperidol to reduced haloperidol plasma levels differed for each ethnic group. These results suggest that various ethnic groups could metabolize haloperidol and reduced haloperidol differently.
Assuntos
Haloperidol/análogos & derivados , Haloperidol/sangue , Negro ou Afro-Americano , População Negra , China , Cromatografia Líquida , Etnicidade , Haloperidol/efeitos adversos , Haloperidol/uso terapêutico , Hispânico ou Latino , Humanos , Escalas de Graduação Psiquiátrica , Radioimunoensaio , Esquizofrenia/tratamento farmacológico , Estados Unidos , População BrancaRESUMO
Seventy DSM-III schizophrenic patients were assessed for positive and negative symptoms using Andreasen's scales for the assessment of positive and negative symptoms (SANS and SAPS) on admission. The correlation structure of the items in the SANS and SAPS was explored in dimension and item levels by use of correlation plots through a distinct analytical method displaying the proximity matrix. The results revealed at least three major dimensions of symptoms delineated as Negative Symptoms, Disorganized Thoughts and Delusions and Hallucinations. The latter two dimensions were derived from the SAPS, while Negative Symptoms comprised most of the items in the SANS. Items in Disorganized Thoughts were more correlated to Negative Symptoms than to the other items in the SAPS. 'Loss of ego boundary' delusions and experience of auditory hallucinations appeared as two sub-clusters in the group of Delusions and Hallucinations. The relative independence of persecutory, grandiose, religious, somatic and reference delusions gives support to the concept that paranoid schizophrenia stands as a distinct clinical subtype of schizophrenia. The graphical method introduced here well expresses the information of correlation matrix and is useful for exploring inter-item or inter-cluster associations.
Assuntos
Testes Psicológicos , Esquizofrenia/diagnóstico , Adolescente , Adulto , Delusões/etiologia , Feminino , Alucinações/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Pensamento/fisiologiaRESUMO
This study examined the relationship between the metabolic ratios of dextromethorphan/dextrorphan, haloperidol disposition, and the incidence of extrapyramidal side effects in schizophrenic patients. Eighteen schizophrenic patients were phenotyped with a test dose of dextromethorphan prior to the initiation of haloperidol treatment. The metabolic ratio of dextromethorphan/dextrorphan was determined in each patient. Patients were treated with oral haloperidol 10 mg/day for 2 weeks. Blood samples for haloperidol and reduced haloperidol were obtained at week 2 of haloperidol treatment. Haloperidol and reduced haloperidol plasma concentrations were assayed by HPLC with electrochemical detection. Significant correlations of dextromethorphan/dextrorphan metabolic ratios vs. plasma haloperidol concentrations, reduced haloperidol concentrations, and reduced haloperidol/haloperidol ratios were found (r = 0.726, P = 0.0007; r = 0.782, P = 0.0001; and r = 0.619, P = 0.006, respectively). Ten patients who experienced extrapyramidal side effects had higher reduced haloperidol concentrations and reduced haloperidol/haloperidol ratios than the other patients (2.49 +/- 1.42 [S.D.] ng/ml vs. 1.10 +/- 0.46 ng/ml, P = 0.014 and 0.287 +/- 0.102 vs. 0.192 +/- 0.065, P = 0.030). The former also had a trend to have higher haloperidol concentrations and dextromethorphan/dextrorphan ratios than the latter (8.04 +/- 2.91 ng/ml vs. 5.83 +/- 1.79 ng/ml, P = 0.066 and 0.023 +/- 0.017 vs. 0.011 +/- 0.010, P = 0.077). Phenotyping patients has the potential to assist clinicians in predicting plasma drug concentrations during the subsequent neuroleptic drug treatment. Further research with phenotyping and psychotropic drug metabolism in psychiatric patients is needed.
Assuntos
Dextrometorfano/farmacocinética , Haloperidol/farmacocinética , Esquizofrenia/metabolismo , Adulto , Povo Asiático , Doenças dos Gânglios da Base/induzido quimicamente , Feminino , Haloperidol/efeitos adversos , Haloperidol/uso terapêutico , Humanos , Masculino , Fenótipo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , População BrancaRESUMO
Plasma reduced haloperidol (RH) concentrations or RH to haloperidol (HL) ratios have been suggested to be important in determining the clinical efficacy and extrapyramidal side effects of HL. In this study, we measured the steady-state plasma HL and RH levels by high performance liquid chromatography and analyzed the effects of various variables (dose, gender, age, and body weight) on RH/HL ratios in four dose groups of Chinese schizophrenic inpatients: 10 mg/day (n = 84), 20 (n = 111), 30 (n = 29), and 60 (n = 55). In addition, the polymorphic distribution of RH/HL ratios, suggested by previous investigators, was further tested in each dosage group (for controlling the potential dosage effect on RH/HL ratios). As a result, both age and body weight could influence RH/HL ratios. Each year increase in age (after adjusting the effects of gender, body weight, and dosage) would elevate the RH/HL ratio by 0.0067 (P < 0.0001). On the other hand, after adjusting gender, age, and dosage effects, each kg increment in body weight would decrease the RH/HL ratio by 0.0044 (P < 0.01). Gender did not influence the ratio. Furthermore, the high dosage groups had higher RH/HL ratios (even with other variables being controlled). In comparison with the 10 mg group, the 60 mg group exhibited a higher mean RH/HL ratio by 0.84 (P < 0.0001) and the 30 mg group did by 0.31 (P < 0.0001). The 20 mg group was almost equal to the 10 mg group in RH/HL ratios. Besides, at each dosage group, the frequency distribution of RH/HL ratios seemed to be predominantly unimodal with a small proportion of extreme outliers. The results of this study clearly indicate that aging or a high dose (> or = 30 mg/day) of HL could raise the plasma RH/HL ratio, while an increasing body weight would reduce that. In contrast, gender does not affect the ratios.
Assuntos
Antipsicóticos/farmacocinética , Discinesia Induzida por Medicamentos/sangue , Haloperidol/análogos & derivados , Haloperidol/farmacocinética , Esquizofrenia/sangue , Adulto , Fatores Etários , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Peso Corporal/fisiologia , Relação Dose-Resposta a Droga , Discinesia Induzida por Medicamentos/diagnóstico , Feminino , Haloperidol/administração & dosagem , Haloperidol/efeitos adversos , Humanos , Masculino , Taxa de Depuração Metabólica/fisiologia , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico , Fatores SexuaisRESUMO
Plasma haloperidol (HAL) and reduced HAL (RHAL) concentrations were measured in 113 Chinese schizophrenic patients. Daily doses of HAL ranged from 8 to 65 mg. Samples were obtained under steady-state conditions and drawn 10-12 hours after the bedtime dose and before the morning dose. In all, 313 blood samples were collected. Multiple samples were obtained at the same doses in 63 patients and at two or three different doses in 31 patients. HAL and RHAL concentrations were assayed by high performance liquid chromatography. Interpatient variation in plasma HAL levels at a given dosage was up to sixfold. However, there was a high positive correlation between plasma levels and daily dosages with the equation of HAL plasma level (ng/ml) = 0.88 x dosage (mg/day) -0.56 or 46.0 x dosage (mg/day/kg) + 0.28. The expected values are about 15-55% higher than those obtained from non-Chinese patients as reported in the literature. The RHAL/HAL ratios were dose-dependent. The greater the dose used, the higher the ratio. An upper therapeutic limit of plasma HAL level is suggested to be 25 ng/ml, which can be achieved at dosages about 30 mg/day in most Chinese patients. Based upon the dose-dependent increase in RHAL/HAL ratios, the importance of RHAL in determining the therapeutic benefit of HAL treatment is discussed.
Assuntos
Haloperidol/sangue , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Interpretação Estatística de Dados , Relação Dose-Resposta a Droga , Feminino , Haloperidol/administração & dosagem , Haloperidol/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Grupos RaciaisRESUMO
Most saturated diacyl phosphatidylcholines C(X):C(Y)PC (saturated 1,2-diacyl-sn-glycero-3-phosphocholine with X carbons in the sn-1 acyl chain and Y carbons in the sn-2 acyl chain), in excess water, can self-assemble into lamellae which, upon heating, may undergo multiple thermotropic phase transitions at well-defined, discrete temperatures. The transition temperature corresponding to the main or the gel to liquid-crystalline phase transition (Tm) is known for many bilayers of fully hydrated phosphatidylcholines. In this study, we have analyzed the Tm values of 44 molecular species of phosphatidylcholines in terms of their structural and packing characteristics in the gel-state bilayer. Two general equations are thus derived: Tm = 162.26-3651.71 (1/N) - 88.42 (delta C/N) for C(X):C(Y)PC with X > or = Y, and Tm = 157.68-3525.44 (1/N) - 93.28 (delta C/N) for C(X):C(Y)PC with X < Y. Here, N is the minimal hydrophobic thickness of the dimeric C(X):C(Y)PC in the gel-state bilayer and delta C is the effective chain length difference between the sn-1 and sn-2 acyl chains for the monomeric C(X):C(Y)PC in the gel-state bilayer. The advantage of these two equations in predicting the Tm values for phosphatidylcholines with delta C/CL values in the range of 0.07 to 0.40 is their simplicity. A figure containing a total of 173 calculated Tm values is also presented.
Assuntos
Temperatura Alta , Bicamadas Lipídicas/química , Fosfatidilcolinas/química , Simulação por Computador , Modelos Moleculares , Temperatura , TermodinâmicaRESUMO
BACKGROUND AND PURPOSE: Zotepine is claimed to be a neuroleptic drug with atypical features. However, there have been few double-blind studies in Asian patients. The purpose of this study was to compare the efficacy and safety of zotepine and haloperidol in Taiwanese patients with schizophrenia. PATIENTS AND METHODS: Patients with positive symptoms (n = 70) were enrolled into this double-blind, randomized study. Each patient received either zotepine 150 mg/day or haloperidol 9 mg/day. The Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI) were assessed on Days 0, 3, 7, 14, 28, and 42 after the start of treatment. Adverse events were recorded during the trial period. The analyses were carried out on an intent-to-treat basis with the last observation carried forward. RESULTS: In terms of the score reduction in the PANSS, BPRS, and CGI, all analyses indicated that there were no significant differences between the groups at the end of the trial. Patients who received zotepine had no acute dystonia and less severe parkinsonism (p < 0.05 or 0.10), but significantly more dizziness, body weight gain, and pulse rate increase. CONCLUSION: In this 6-week trial, zotepine at 150 mg/day was as efficacious as haloperidol 9 mg/day in the treatment of Taiwanese patients with schizophrenia. Zotepine treatment produced fewer extrapyramidal symptoms but had a greater frequency of sedative effects compared to haloperidol.