AIMTo study a continuous, on-line and automatic monitoring method for dissolution of drugs.

METHODSA new fiber optical chemical sensor prepared by sol-gel immobilization of molecular probe was reported. Based on multiple quenching of flurescence, an instrument and software system was designed to on-line monitor the drug dissolution of rifampicin.

RESULTSThe concentration of rifampicin was linear with ln(F0/F) when concentration was in the range of 10-170 micrograms/mL-1. The relative coefficient was 0.9993. The procession of dissolution can be on-line monitored. Parameters were obtained directly from the dissolution curve. There is no distinctly difference when compared with the method of the Pharmacopoeia of People's Republic of China (P > 0.05).

CONCLUSIONThis procession analysis can reflect the real dissolution of drug and obtain the total information.

Antibiotics, Antitubercular ; administration & dosage ; chemistry ; Automatic Data Processing ; Capsules ; Rifampin ; administration & dosage ; chemistry ; Solubility

Rifampin, when given in usual doses, is well tolerated with less than 4% of patients having significant adverse reactions. The patient had did not have any adverse reaction to rifampin in the first place. After 10 years, however, the patient was presented with hypotension, shortness of breath, wheezing and deterioration of consciousness in 10 minutes after taking rifampin. All abnormal symptoms and signs of anaphylaxis were normalized in 24 hours after administration of normal saline, glucocorticosteroid, and antihistamine. Skin prick test with rifampin showed positive reaction to gradual concentration of rifampin in dose dependent manner. The wheals by rifampin developed in 30 minutes and maximized in 2 hours, while normal saline and histamine controls showed expected negative and positive response in 10 minutes, respectively. Recently we expererienced a rare case of anaphylaxis after single oral administration of rifampin (450mg), who had been treated with antituberculous drug including rifampin, ca 10 years ago.
Administration, Oral ; Anaphylaxis* ; Consciousness ; Dyspnea ; Histamine ; Humans ; Hypotension ; Respiratory Sounds ; Rifampin* ; Skin

Tuberculosis (TB) is prevalent and remains a major public health problem in South Korea. Joint committee for the development of Korean guidelines for TB has published a guideline for the treatment of TB recently. The aim of this guideline is to provide evidence based practical recommendations to clinicians caring TB patients in South Korea. Treatment regimen for the newly diagnosed TB is divided into 2 months of initial intensive phase (isoniazid, rifampin, ethambutol, pyrazinamide) followed by 4 months of maintenance phase (isoniazid, rifampin, ethambutol). Ethambutol may be dropped from the regimen after 2 months of treatment if bacilli is susceptible to isoniazid and rifampin (2HREZ/4HR). Because stopping medical treatment by the patient is most serious problem in the treatment of TB, this guideline emphasizes education and supervision of the patients to ensure patient's adherence to taking medicines.
Dietary Sucrose ; Ethambutol ; Humans ; Isoniazid ; Joints ; Organization and Administration ; Public Health ; Republic of Korea ; Rifampin ; Tuberculosis

Primary biliary cirrhosis (PBC) is a chronic cholestatic autoimmune liver disease that predominantly affects middle-aged women. It is characterized by slowly progressive destruction of the small intrahepatic bile ducts together with portal inflammation, and this initially leads to fibrosis and later to cirrhosis. It is currently accepted that the pathogenesis of PBC is multifactorial with genetic and environmental factors interplaying to determine the disease onset and progression. In addition to antimitochondrial antibody (AMA), which is the hallmark of PBC and is detected in at least 90% of the patients, other autoantibodies (antinuclear antibody, anti-smooth muscle antibody and rheumatoid factor, etc.) may also be found in the patients. There is no correlation between the titer of AMAs and the disease severity. Most patients are diagnosed either during the asymptomatic phase of PBC or after presenting with non-specific symptoms. Pruritus and fatigue are the most common symptoms of PBC. The prognosis of PBC has improved significantly during the last few decades. Patients are now diagnosed earlier in its clinical course, they are more likely to be asymptomatic at diagnosis and they are more likely to receive medical treatment. A wide variety of drugs have been assessed for the treatment of this condition: such immunosuppressive agents as corticosteroids, cyclosporine and azathioprine have a weak effect on the disease's natural history. Ursodeoxycholic acid (UDCA) is the only currently approved medical treatment. For PBC patients with end-stage liver disease or an unacceptable quality of life, liver transplantation is the only accepted therapeutic option. Early diagnosis and treatment of PBC are important because effective treatment with UDCA has been shown to delay disease progression and improve rate survival in the early stage.
Autoimmune Diseases/*diagnosis/*drug therapy/epidemiology ; Cholagogues and Choleretics/*therapeutic use ; Cholestadienes/administration & dosage/therapeutic use ; Cholic Acids/administration & dosage/therapeutic use ; Female ; Humans ; Liver Cirrhosis, Biliary/*diagnosis/*drug therapy/epidemiology ; Male ; Middle Aged ; Prevalence ; Rifampin/administration & dosage/therapeutic use

Atopic dermatitis (AD) is a common inflammatory skin disorder mediated by inflammatory cells, such as macrophages and mast cells. Rifampicin is mainly used for the treatment of tuberculosis. Recently, it was reported that rifampicin has anti-inflammatory and immune-suppressive activities. In this study, we investigated the effect of rifampicin on atopic dermatitis in vivo and in vitro. AD was induced by treatment with 2, 4-dinitrochlorobenzene (DNCB) in NC/Nga mice. A subset of mice was then treated with rifampicin by oral administration. The severity score and scratching behavior were alleviated in the rifampicin-treated group. Serum immunoglobulin E (IgE) and interleukin-4 (IL-4) levels were also ameliorated in mice treated with rifampicin. We next examined whether rifampicin has anti-atopic activity via suppression of mast cell activation. Rifampicin suppressed the release of β-hexosaminidase and histamine from human mast cell (HMC)-1 cultures stimulated with compound 48/80. Treatment with rifampicin also inhibited secretion of inflammatory mediators, such tumor necrosis factor-α (TNF-α) and prostaglandin D₂ (PGD₂), in mast cells activated by compound 48/80. The mRNA expression of cyclooxygenase 2 (COX-2) was reduced in the cells treated with rifampicin in a concentration-dependent manner. These results suggest that rifampicin can be used to treat atopic dermatitis.
Administration, Oral ; Animals ; Cyclooxygenase 2 ; Dermatitis, Atopic ; Histamine ; Humans ; Immunoglobulin E ; Immunoglobulins ; In Vitro Techniques* ; Interleukin-4 ; Macrophages ; Mast Cells ; Mice ; Necrosis ; Rifampin* ; RNA, Messenger ; Skin ; Tuberculosis

Atopic dermatitis (AD) is a common inflammatory skin disorder mediated by inflammatory cells, such as macrophages and mast cells. Rifampicin is mainly used for the treatment of tuberculosis. Recently, it was reported that rifampicin has anti-inflammatory and immune-suppressive activities. In this study, we investigated the effect of rifampicin on atopic dermatitis in vivo and in vitro. AD was induced by treatment with 2, 4-dinitrochlorobenzene (DNCB) in NC/Nga mice. A subset of mice was then treated with rifampicin by oral administration. The severity score and scratching behavior were alleviated in the rifampicin-treated group. Serum immunoglobulin E (IgE) and interleukin-4 (IL-4) levels were also ameliorated in mice treated with rifampicin. We next examined whether rifampicin has anti-atopic activity via suppression of mast cell activation. Rifampicin suppressed the release of β-hexosaminidase and histamine from human mast cell (HMC)-1 cultures stimulated with compound 48/80. Treatment with rifampicin also inhibited secretion of inflammatory mediators, such tumor necrosis factor-α (TNF-α) and prostaglandin D₂ (PGD₂), in mast cells activated by compound 48/80. The mRNA expression of cyclooxygenase 2 (COX-2) was reduced in the cells treated with rifampicin in a concentration-dependent manner. These results suggest that rifampicin can be used to treat atopic dermatitis.
Administration, Oral ; Animals ; Cyclooxygenase 2 ; Dermatitis, Atopic ; Histamine ; Humans ; Immunoglobulin E ; Immunoglobulins ; In Vitro Techniques* ; Interleukin-4 ; Macrophages ; Mast Cells ; Mice ; Necrosis ; Rifampin* ; RNA, Messenger ; Skin ; Tuberculosis

OBJECTIVETo fabricate a new composite scaffold material as an implant for sustained delivery of rifampicin and evaluate its performance of sustained drug release and biocompatibility.

METHODSThe composite scaffold material was prepared by loading poly(lactic-co-glycolic) acid (PLGA) microspheres that encapsulated rifampicin in a biphasic calcium composite material with a negative surface charge. The in vitro drug release characteristics of the microspheres and the composite scaffold material were evaluated; the in vivo drug release profile of the composite scaffold material implanted in a rat muscle pouch was evaluated using high-performance liquid chromatography. The biochemical parameters of the serum and liver histopathologies of the rats receiving the transplantation were observed to assess the biocompatibility of the composite scaffold material.

RESULTSThe encapsulation efficiency and drug loading efficiency of microspheres were (56.05±5.33)% and (29.80±2.88)%, respectively. The cumulative drug release rate of the microspheres in vitro was (94.19±5.4)% at 28 days, as compared with the rate of (82.23±6.28)% of composite scaffold material. The drug-loaded composite scaffold material showed a good performance of in vivo drug release in rats, and the local drug concentration still reached 16.18±0.35 µg/g at 28 days after implantation. Implantation of the composite scaffold material resulted in transient and reversible liver injury, which was fully reparred at 28 days after the implantation.

CONCLUSIONThe composite scaffold material possesses a good sustained drug release capacity and a good biocompatibility, and can serve as an alternative approach to conventional antituberculous chemotherapy.

Animals ; Biocompatible Materials ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; chemistry ; Drug Liberation ; Lactic Acid ; chemistry ; Microspheres ; Polyglycolic Acid ; chemistry ; Rats ; Rifampin ; administration & dosage

Rifampin is commonly used as a first-line anti-tuberculosis drug, but it can induce a serum sickness-like reaction or anaphylaxis. However, it is possible for 1 drug antigen to induce 2 or more simultaneous immunologic reactions. Here, we report a case of a serum-sickness-like reaction and anaphylaxis induced concurrently by rifampin. A 25-year-old male presented with high fever and a maculopapular rash with vesicles on the hands, which developed 2 weeks following regular administration of anti-tuberculosis drugs for tuberculous meningitis, including rifampin. Elevated liver enzymes, peripheral neuropathy, and decreased serum C3 and C4 levels were found. Interestingly, these symptoms were accompanied by severe hypotension. A serum-sickness-like reaction was considered after excluding other potential causes for the fever. A drug provocation test showed that the fever developed after oral administration of rifampin, suggesting that rifampin was the cause of the allergic reaction. However, hypotension, epigastric discomfort, and diarrhea also accompanied these symptoms, indicating that IgE-mediated type I hypersensitivity could be part of the serum sickness-like reaction. An intradermal skin test clearly showed an immediate positive reaction to rifampin. This case was diagnosed as concurrent serum-sickness-like reaction and anaphylaxis induced by rifampin. One drug may therefore induce combined allergic reactions via 2 or more simultaneous hypersensitivity responses.
Administration, Oral ; Adult ; Anaphylaxis* ; Diarrhea ; Exanthema ; Fever ; Hand ; Humans ; Hypersensitivity ; Hypersensitivity, Immediate ; Hypotension ; Liver ; Male ; Peripheral Nervous System Diseases ; Rifampin* ; Skin Tests ; Tuberculosis, Meningeal

BACKGROUNDDecreases in the bioavailability of rifampicin (RFP) can lead to the development of drug resistance and treatment failure. Therefore, we investigated the relative bioavailability of RFP from one four-drug fixed-dose combination (FDC; formulation A) and three two-drug FDCs (formulations B, C, and D) used in China, compared with RFP in free combinations of these drugs (reference), in healthy volunteers.

METHODSEighteen and twenty healthy Chinese male volunteers participated in two open-label, randomized two-period crossover (formulations A and C) or one three-period crossover (formulations B and D) study, respectively. The washout period between treatments was 7 days. Bioequivalence was assessed based on 90% confidence intervals, according to two one-sided t-tests. All analyses were done with DAS 3.1.5 (Mathematical Pharmacology Professional Committee of China, Shanghai, China).

RESULTSMean pharmacokinetic parameter values of RFP obtained for formulations A, B, C, and D products were 11.42 ± 3.41 μg/ml, 7.86 ± 5.78 μg/ml, 13.05 ± 6.80 μg/ml, and 16.18 ± 3.87 μg/ml, respectively, for peak plasma concentration (C max ), 91.43 ± 30.82 μg·h-1·ml-1 , 55.49 ± 37.58 μg·h-1·ml-1 , 96.50 ± 47.24 μg·h-1·ml-1 , 101.47 ± 33.07 μg·h-1·ml-1 , respectively, for area under the concentration-time curve (AUC 0-24 h ).

CONCLUSIONSAlthough the concentrations of RFP for formulations A, C, and D were within the reported acceptable therapeutic range, only formulation A was bioequivalent to the reference product. The three two-drug FDCs (formulations B, C and D) displayed inferior RFP bioavailability compared with the reference (Chinese Clinical Trials registration number: ChiCTR-TTRCC-12002451).

Adult ; Asian Continental Ancestry Group ; Biological Availability ; Drug Combinations ; Humans ; Male ; Rifampin ; administration & dosage ; pharmacokinetics ; therapeutic use ; Tuberculosis ; drug therapy ; Young Adult

Anti-Inflammatory Agents ; administration & dosage ; Arthritis ; diagnosis ; drug therapy ; etiology ; physiopathology ; Arthritis, Rheumatoid ; diagnosis ; Clofazimine ; administration & dosage ; Dapsone ; administration & dosage ; Delayed Diagnosis ; Diagnosis, Differential ; Humans ; Leprostatic Agents ; administration & dosage ; Leprosy ; complications ; diagnosis ; drug therapy ; physiopathology ; Male ; Middle Aged ; Prednisolone ; administration & dosage ; Rifampin ; administration & dosage ; Treatment Outcome