RESUMO
Genital herpes simplex virus (HSV) infection, a sexually transmitted disease (STD), is the commonest cause of ulcerative genital infections among the young and adult population. The significant association of genital ulceration and transmission of human immunodeficiency virus (HIV) has been shown in many studies. To explore the potential efficacy of topical treatment of genital herpes with penciclovir cream, a randomized, double-blind, multicentre, acyclovir-controlled Phase II clinical trial of penciclovir 1% cream 5 times daily up to 7 days for suppression of genital herpes was conducted in China. A total of 205 patients aged 20-59 years (mean age 36.0+/-8.8 years for acyclovir and 34.8+/-8.4 years for penciclovir) with a clinical diagnosis of genital herpes were randomly allocated to one of the 2 parallel treatment groups and used for analysis. Clinical assessment were made before treatment and followed up at every visit during the study. Our results show that there was an encouraging improvement simultaneously in the 2 groups although no significant differences in clinical efficacy with respect to clinical cure rate, and times to healing, resolution of all symptoms, absence of blisters, cessation of new blisters, crusting, and loss of crust between penciclovir and acyclovir groups in terms of primary, non-primary and total patients were found. However a significantly shorter time to crusting was found in primary penciclovir group when compared with primary acyclovir group. Adverse experience was generally infrequent and mild, and was comparable in the 2 treatment groups. Based on these preliminary clinical findings, further evaluation of penciclovir 3% cream for topical treatment of genital herpes is planned.
Assuntos
Aciclovir/análogos & derivados , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Herpes Genital/tratamento farmacológico , Aciclovir/administração & dosagem , Aciclovir/efeitos adversos , Administração Tópica , Adulto , Antivirais/administração & dosagem , Antivirais/efeitos adversos , China , Método Duplo-Cego , Feminino , Seguimentos , Guanina , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: To develop an HPLC assay for simultaneous determination of AD202 and its metabolites and to examine metabolites of AD202 in urine of rats. METHODS: Reverse-phase HPLC with fluorescence detection and gradient elutionusing a Waters Chromatograph equipped with a 710 B WIFP autosampler, a power Mate SX plus computer, C18 Nova-pak (4 microns) 5 mm x 10 cm radial compression column connected with a guard micro-column, and a Waters 991 photodiode array detector for online observation of UV spectrum of related fraction. RESULTS: Detection limit was 1-3 ng for AD202 and 1-3 ng for its metabolites per injection. After i.v. AD202 20 mg.kg-1, only 4.9% dose as total anthracycline fluorescence signal was recovered in urine over 72 h. The predominant urinary metabolites were AD285 (desacyl AD202) and AD284 (N-mono-debutyl AD285). Six minor metabolites including aglycones and 13-keto reductive product were identified and 3 as-yet unknown metabolites were seen. Enzymatic and acid-hydrolysis failed to reveal the presence of glucuronides in urine. CONCLUSION: The sample analysis techniques developed in this study proved to be very efficient, sensitive, and specific, a total of 11 compounds achieved resolution with detection limit of 2 ng and no interference from matrix. Urine samples can be injected directly into chromatograph without any extraction, making sample analysis simple and time-saving.
Assuntos
Antibióticos Antineoplásicos/urina , Doxorrubicina/análogos & derivados , Animais , Antibióticos Antineoplásicos/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Doxorrubicina/farmacocinética , Doxorrubicina/urina , Feminino , Ratos , Ratos Sprague-DawleyRESUMO
Placental villus tissue obtained from pregnant women of 6 to 7 weeks was cultured in vitro for four days, with or without addition of tamoxifen (Tam), an antiestrogenic drug. The levels of both progesterone (P) and human chorionic gonadotropin (hCG) in culture medium collected every day were measured by using radio-immuno assay, so as to observe the effects of Tam on the secretion of P and hCG by villus tissue as well as the time course of these effects. The experimental results showed that the levels of both P and hCG in the culture medium collected on the 3rd and 4th days in the Tam-treated group were significantly lower than those in the control group, indicating that Tam could have a direct inhibitory effect on the secretory function of the placental villus tissue during early pregnancy. The slow onset of the inhibitory effect was in correspondence with the clinical observation that the early pregnancy terminating effect of PGS would be potentiated after 4-5 days of Tam medication. In addition, this inhibitory effect of tamoxifen on the placental secretory function was suggested to be associated with a decrease in the responsiveness of placental tissue to GnRH.
Assuntos
Gonadotropina Coriônica/metabolismo , Vilosidades Coriônicas/metabolismo , Progesterona/metabolismo , Tamoxifeno/farmacologia , Vilosidades Coriônicas/efeitos dos fármacos , Feminino , Hormônio Liberador de Gonadotropina/farmacologia , Humanos , Gravidez , Primeiro Trimestre da GravidezRESUMO
A reversed-phase HPLC method for determination of isotetrandrine (ITD) in biological specimens was developed. The mobile phase composed of 0.2% (w/v) SDS, 47% acetonitrile and 53% distilled water (pH 2), at a flow rate of 1.5 ml/min with determination wavelength of 230 nm. The drug concentration-time curves of ITD in rats after iv of 12.5, 25 and 50 mg/kg were shown to fit a two-compartment open model with half-lives of 67.1 +/- 6.22 68.0 +/- 2.57 and 97.6 +/- 14.6 min, respectively. At doses of 12.5 and 25 mg/kg, the elimination of the drug from plasma was found to be in accord with linear kinetics, but when the dosage was 50 mg/kg, a non-linear kinetics was observed. Following ig ITD 100 and 250 mg/kg, the plasma concentration-time curves exhibited two marked peaks. Half-lives of elimination after ig doses was much longer than after iv administration, with mean values of 9.35 +/- 3.24 h (100 mg/kg) and 9.01 +/- 3.02 h (250 mg/kg). Distribution of the drug in rats was extensive, highest level of the drug was found in the lung and lowest in plasma after iv administration. Following ig administration, highest level of the drug was found in the liver and lowest in plasma.
Assuntos
Alcaloides/farmacocinética , Anti-Inflamatórios não Esteroides/farmacocinética , Antineoplásicos Fitogênicos/farmacocinética , Benzilisoquinolinas , Animais , Cromatografia Líquida de Alta Pressão/métodos , Masculino , Ratos , Ratos Endogâmicos , Estereoisomerismo , Distribuição TecidualRESUMO
It has been found that in rats exposed to a noise of 2kHz (mai frequency) and 103 dB(A) (potency) for 60 minutes, the hepatic glycogen content (HGC) is significantly higher than that of the control group unexposed to the noise (P less than 0.05), whereas in those treated with a prior ip Radix Astragali plus noise the HGC appears apparently lower than that of the noise group (P less than 0.05), very close to the control group (P greater than 0.2). This indicates that Radix Astragali might have some antinoise effect.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Glicogênio Hepático/metabolismo , Ruído/efeitos adversos , Animais , Injeções Intraperitoneais , Fígado/metabolismo , Masculino , RatosAssuntos
Glucosídeos/farmacocinética , Glicosídeos/farmacocinética , Animais , Álcoois Benzílicos/análise , Álcoois Benzílicos/farmacocinética , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/métodos , Cães , Feminino , Glucosídeos/análise , Masculino , Coelhos , Ratos , Especificidade da Espécie , Distribuição TecidualRESUMO
A rapid and specific HPLC method for the simultaneous determination of gastrodin and its metabolite gastrodigenin (p-hydroxybenzyl alcohol) in rat plasma, bile, liver, urine and faeces is described. The separation was achieved by using a reversed phase column (YWG-C18) eluted with methanol-water (2.5:97.5 v/v). Phloroglucinolum was used as internal standard and the peaks were detected at UV 221 nm. The protein precipitation with ethanol was a very simple and rapid method for sample preparation. The gastrodin and gastrodigenin were quantitated by measuring the peak-height ratios. There was a linear concentration range of 10-320 micrograms/mL in the assay for both compounds. The coefficients of variation (within-day) for samples spiked with gastrodin and gastrodigenin were 2.94% and 3.08%, respectively. The method demonstrated a high specificity and was suitable for use in pharmacokinetic studies.