Tinidazole (Fasigyn), a new drug which is active in vitro and in vivo against Entamoeba histolytica, was used in 30 Korean patients with acute and chronic intestinal amoebiasis. In aute amoebic dysentry eight of ten patients given tinidazole 150 mg q.i.d. for 10 days were cured clinically and parasitologically. In chronic intestinal amoebiasis, the parasitological cure was obtained 6 out of 10 patients given150 mg q.i.d. for 10 days and 8 out of 10 in patients given 300 mg q.i.d. for 7 days. Tinidazole is well tolerated and is free from serious toxicity. There was no significant alteration in blood count, liver function tests and urine analysis of any of the patients treated with tinidazole.
parasitology-protozoa-Entamoeba histolytica ; chemotherapy-Tinidazole ; drug ; Tinidazole

OBJECTIVETo determine the dynamic release of tinidazole from the degradable poly-lactic acid (PLLA)-tinidazole blend gel (a periodontal local drug delivery) by high-performance liquid chromatography (HPLC) in vitro and to observe the polylactic acid (as a vector of tinidazole) how to affect the release of tinidazole.

METHODSHPLC analysis was conducted. The operating conditions were C18-ODS-A column, water-methanol-acetic acid as mobile phase at a flow rate of 1.5 ml/min and a detection wavelength at 310 nm and a column temperature at 30 degrees C.

RESULTSThe retention time of tinidazole was about 12 min. There was good linear relationship between the concentrations of tinidazole in blend gel and their peak areas in the ranges of 5 - 500 mg/L. The regression reaction was y = 0.836 + 8.452 2 x 10(-5) x (r = 0.998 6). RSD was 0.2%. Polylactic acid had no influence on the determination of tinidazole. The daily average release of tinidazole was 5.60%. The cumulative release of tinidazole was about 78.40% in 14 days.

CONCLUSIONThe in vitro drug release analysis is an useful method in evaluating the performance of local drug delivery system. HPLC analysis is a simple and accurate method with good reproducibility.

Chromatography, High Pressure Liquid ; Lactic Acid ; Polyesters ; Polymers ; Reproducibility of Results ; Tinidazole

AIMTo illustrate the non-equilibrium properties of drug permeation through stratum corneum (SC) to provide theory and method for transdermal drug delivery.

METHODSThe system of side-by-side permeation chambers in vitro was isolated, thus conditions for equilibrium state were decided. And a network thermodynamic model was established. Non-equilibrium and leakage experiments were completed with which tinidazole was pattern drug.

RESULTSThe properties of non-equilibrium including: long term to reach equilibrium state; delay-start of the permeation; uncertainty of initial drug permeable flux. The properties of leakage including: degression of drug permeable flux; changeability of permeation time constant.

CONCLUSIONThe permeation cell is believed to be a non-linear and time variable system.

Administration, Cutaneous ; Electroporation ; Epidermis ; metabolism ; Humans ; In Vitro Techniques ; Permeability ; Tinidazole ; administration & dosage ; pharmacokinetics

The objective of this study was to prepare a biodegradable poly (DL-lactide) injectable gel of tinidazole. The formulation parameters evaluated in this study included polymer molecular weight, polymer concentration, solvent and drug loading, and orthogonal design was used to optimize the formulation. The preferable formulation was that 30% (w/w) poly(DL-lactide) (MW is 5 700) dissolved in 70% (w/w) N-methyl-2-pyrrolidone with 4%-6% (w/w) tinidazole.
Delayed-Action Preparations ; Drug Carriers ; chemistry ; Gels ; Lactic Acid ; chemistry ; Polyesters ; Polymers ; chemistry ; Technology, Pharmaceutical ; methods ; Tinidazole ; administration & dosage

BACKGROUND: We thought that nitroimidazoles including metronidazole had been overused empirically for treatment of trichomoniasis in Korea. But there were not any reports about in vitro-drug susceptibility and distribution of resistant strains of Trichomonas vaginalis up to date. Therefore, we made an experiment in order to observe the susceptibility of clinical isolates of T. vaginalis to a variety of antiprotozoal agents. METHODS: Twenty-six strains of T. vaginalis isolated from 217 patients afflicted with the increased vaginal discharge were tested by Meingassner's microtiter plate method in newly devised anaerobic box, in which anaerobic and microaerobic conditions were more easily manipulated. The agents used in this study for testing the minimal lethal concentration (MLC) to the clinical isolates were as follows; nitroimidazoles, doxycycline, Zinc sulfate and gentian violet as chemotherapeutic agents and povidone-iodine as vaginal cleansing agents were studied. RESULTS: In anaerobic culture, according to anaerobic resistance cut-point (minimal lethal concentration >3.1 microgram/mL) proposed by M ller etc., metronidazole (MTZ)-, tinidazole (TNZ)-and ornidazole (ONZ)-resistant strains were four (4/26, 15.4%), two (2/26, 7.7 %) and two (2/26, 7.7%) strains, respectively. Among these resistant strains, two strains (G7 and G16) were resistant to two drugs and one strain (G20) resistant to three drugs concomitantly. Their resistance range was narrow as 6.25~12.5 microgram/mL. MLC of clotrimazole was > or = 2,000 microgram/mL in all strains, econazole was as high as 62.5~250 microgram/mL and miconazole was also high as 62.5~> or = 2,000 microgram/mL. In microaerobic culture (O2 concentration <5%), all strains showed lower MLC to MTZ, TNZ and ONZ than >100 microgram/ mL (aerobic resistance cut-point proposed by M ller etc.). MLC of doxycycline ranged 62.5 to 250 microgram/mL both in microaerobic and anaerobic conditions. All strains of T. vaginalis growed well in 3,000 microgram/mL of povidone-iodine. 22 strains (84.6%) among 26 T. vaginalis strains showed MLCs of 3.5 mM~7.0 mM to zinc sulfate. Gentian violet showed 15.6~62.5 microgram/mL of MLC. CONCLUSION: In absolute anaerobic culture, 4 strains (15.4%) among 26 T. vaginalis strains were resistant to metronidazole. But these 4 strains were not resistant in microaerobic culture depending on Miler's aerobic resistance cut-point (>50~100 microgram/mL), the value decided in normal O2 pressure. Vaginal PO2 is 0~28mm Hg (median 1 mmHg) at healthy or trichomonas-infected women. Therefore, we think that his aerobic resistance cut-point value is hard to be available in microaerobic condition and microaerobic resistance guide-line is to be established newly.
Anti-Infective Agents ; Antiprotozoal Agents* ; Clotrimazole ; Detergents ; Doxycycline ; Econazole ; Female ; Gentian Violet ; Humans ; Korea ; Metronidazole ; Miconazole ; Nitroimidazoles ; Ornidazole ; Povidone-Iodine ; Tinidazole ; Trichomonas vaginalis* ; Trichomonas* ; Vaginal Discharge ; Zinc Sulfate

This review dealt with biology, host-parasite relationship, symptomatology, epidemiology, diagnosis, treatment of Entamoeba histolytica infection and free livng amoeba.
parasitology-protozoa ; Entamoeba histolytica ; Entabmoeba gingivalis ; Trichomonas tenax ; Naegleria sp. ; Naegleria fowleri ; Acanthamoeba lenticulata ; Acanthamoeba sp. ; biology ; epidemiology ; diagnosis ; chemotherapy ; metronidazole ; onidazole ; tinidazole

BACKGROUND: To the best of our knowledge, there has been no any report on the antibiotic susceptibility profile of Gardnerella vaginalis, determined in domestic area by the agar dilution method. Therefore, we studied on 49 strains of G. vaginalis by the agar dilution method. METHODS: One standard strain (ATCC 14018) and Forty-eight strains isolated from patients with increased vaginal discharge were included in this study. Columbia agar base containing 1% proteose peptone No. 3 was supplemented with horse serum (5%) and human erythrocyte lysate (5%) which was prepared by a new method, and this medium was used for the antibiotic susceptibility test. RESULTS: The MICs90 of clindamycin and ciprofloxacin were 0.3 g/mL and 0.6 g/mL, respectively. Amoxicillin, cefazolin, doxycycline, and erythromycin were hardly effective against most strains of G. vaginalis (NCCLS, U.S.A., 2001). Especially, MICs90 of both metronidazole and tinidazole were 80 g/ mL under micro-aerobic condition of 5% O2. CONCLUSION: For the treatment of Bacterial vaginosis, it is suggested that clindamycin or ciprofloxacin should be combined with vaginal tablet or gel of metronidazole rather than single administration of metrondazole or tinidazole.
Agar* ; Amoxicillin ; Cefazolin ; Ciprofloxacin ; Clindamycin ; Doxycycline ; Drug Resistance ; Erythrocytes* ; Erythromycin ; Gardnerella vaginalis* ; Gardnerella* ; Horses* ; Humans* ; Metronidazole ; Peptones ; Tinidazole ; Vaginal Creams, Foams, and Jellies ; Vaginal Discharge ; Vaginosis, Bacterial

BACKGROUND: To the best of our knowledge, there has been no any report on the antibiotic susceptibility profile of Gardnerella vaginalis, determined in domestic area by the agar dilution method. Therefore, we studied on 49 strains of G. vaginalis by the agar dilution method. METHODS: One standard strain (ATCC 14018) and Forty-eight strains isolated from patients with increased vaginal discharge were included in this study. Columbia agar base containing 1% proteose peptone No. 3 was supplemented with horse serum (5%) and human erythrocyte lysate (5%) which was prepared by a new method, and this medium was used for the antibiotic susceptibility test. RESULTS: The MICs90 of clindamycin and ciprofloxacin were 0.3 g/mL and 0.6 g/mL, respectively. Amoxicillin, cefazolin, doxycycline, and erythromycin were hardly effective against most strains of G. vaginalis (NCCLS, U.S.A., 2001). Especially, MICs90 of both metronidazole and tinidazole were 80 g/ mL under micro-aerobic condition of 5% O2. CONCLUSION: For the treatment of Bacterial vaginosis, it is suggested that clindamycin or ciprofloxacin should be combined with vaginal tablet or gel of metronidazole rather than single administration of metrondazole or tinidazole.
Agar* ; Amoxicillin ; Cefazolin ; Ciprofloxacin ; Clindamycin ; Doxycycline ; Drug Resistance ; Erythrocytes* ; Erythromycin ; Gardnerella vaginalis* ; Gardnerella* ; Horses* ; Humans* ; Metronidazole ; Peptones ; Tinidazole ; Vaginal Creams, Foams, and Jellies ; Vaginal Discharge ; Vaginosis, Bacterial

PURPOSE: In a previous study, we have shown that anticancer agents inhibiting topoisomerases improve survival of tumor cells under hypoxic condition. In the present study, we evaluated whether and how cell survival effect of the anticancer agents under hypoxic conditions could be eliminated by the addition of nitroimidazoles, a class of bioreductive agents. METHODS: Human hepatocellular carcinoma cells (HepG2) were incubated with different combinations of pimonidazole (1~1,000 microg/ml) and doxorubicin (0.1 or 1 microg/ml) concentrations under different O2 concentrations [1, 3, 5, 10 and 21 O2]. Then cell numbers, glucose concentrations and lactic acid concentrations in the medium were measured, and DNA fragmentation assay was performed. Finally, different combinations of nitroimidazoles, such as pimonidazole, misonidazole, etanidazole, tinidazole, metronidazole, ornidazole or dimetridazole, and anticancer agents, such as doxorubicin, campothecin, epirubicin, dactinomycin, etoposide or mitomycin C was added to the cell culture medium under hypoxic conditions (1% O2). RESULTS: Pimonidazole at a concentration of 100 microg/ml eliminated cell survival effect of doxorubicin at the concentrations of 0.1 and 1 microg/ml under hypoxic condition (1% O2) by promoting apoptosis. Almost all the cells died even after 24 hours of incubation for all the oxygen concentrations at a combination of 100 microg/ml pimonidazole and 1 microg/ml doxorubicin. Finally, pimonidazole at a concentration of 100 microg/ml, and misonidazole or etanidazole at a concentration of 1,000 microg/ml eliminated cell survival effect of all the anticancer agents tested under hypoxic condition. CONCLUSION: Combination therapy of doxorubicin (adriamycin) with pimonidazole can maximize dororubicin efficacy by eliminating cell survival effect of doxorubicin under hypoxic conditions in treating solid tumors, such as breast cancer.
Anoxia ; Antineoplastic Agents ; Apoptosis ; Breast Neoplasms ; Carcinoma, Hepatocellular ; Cell Count ; Cell Culture Techniques ; Cell Survival ; Dactinomycin ; Dimetridazole ; DNA Fragmentation ; Doxorubicin ; Epirubicin ; Etanidazole ; Etoposide ; Glucose ; Humans ; Lactic Acid ; Metronidazole ; Misonidazole ; Mitomycin ; Nitroimidazoles ; Ornidazole ; Oxygen ; Tinidazole

AIMTo test the enhancing activity and the mechanism of oleyl pyroglutamate used as transdermal enhancer.

METHODSThe penetration-enhancing effects of oleyl pyroglutamate, oleyl alcohol and oleic acid on the three drugs (caffeine, tinidazole and cortisone) were observed; the transdermal enhancing mechanism of oleyl pyroglutamate was studied with the attenuated total reflectance Fourier-transfer infrared spectroscopy(ATR-FTIR) of the human stratum corneum in vivo.

RESULTSThe penetration-enhancing ratio of the three drugs was 7.9 fold, 41.8 fold and 2.8 fold, respectively. The absorptions at 2,800-2,950 cm-1 and 1,642-1,646 cm-1 (amide-I) in the ATR-FTIR spectrum of the stratum were found to be shifted differently following removal of the stratum corneum which was treated with oleyl pyroglutamate.

CONCLUSIONOleyl pyroglutamate showed better penetration-enhancing effect on the penetration of drugs. Its transdermal enhancing mechanism may be that oleyl pyroglutamate induced not only disordering of the stratum corneum lipid, but also change of the secondary structure of keratin.

Administration, Cutaneous ; Adult ; Animals ; Caffeine ; administration & dosage ; pharmacokinetics ; Cortisone ; administration & dosage ; pharmacokinetics ; Fatty Alcohols ; pharmacology ; Humans ; Male ; Mice ; Oleic Acid ; pharmacology ; Pyrrolidonecarboxylic Acid ; analogs & derivatives ; chemistry ; pharmacology ; Skin Absorption ; drug effects ; Tinidazole ; administration & dosage ; pharmacokinetics