rifampin and Dizziness

Although cytochrome P450 (CYP) 2D6 is often thought to be the only CYP responsible for the metabolism of risperidone, many reports suggest that CYP3A may be involved too. Rifampin, a potent CYP3A inducer, has been known to markedly decrease plasma concentrations of various drugs, which are concomitantly administered during treatment.. To examine the effect of rifampin on plasma concentrations of a single oral dose of risperidone in healthy Thai male volunteers.. In an open, randomized two-phase crossover study, separated by a 2-week period, 10 healthy Thai male volunteers received a single oral dose of 4-mg risperidone alone or with 600 mg rifampin, orally once daily for 5 days. Serial blood samples were collected at specific time points for a 48-h period. Risperidone was measured in plasma using high performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined by using non-compartmental analysis.. Co-administration with 600-mg rifampin once daily for 5 days was associated with a significant decrease in risperidone area under the curve (AUC(0-48)) and maximal concentration (C(max)) by 72% (157 x 49 +/- 48 x 80 vs. 42 x 66 +/- 7 x 81 ng/L/h; P<0 x 01) and 50% (32 x 44 +/- 6 x 05 vs. 16 x 16 +/- 2 x 73 ng/mL; P<0 x 05), respectively when compared with risperidone alone.. Rifampin when used concurrently with risperidone significantly decreases the plasma concentration of risperidone. Our results provide in vivo evidence of the involvement of CYP3A in the metabolism of risperidone, in addition to CYP2D6. Thus, co-administration of risperidone with CYP3A inducer(s), including rifampin should be recognized or avoided in clinical practice.

Topics: Administration, Oral; Adult; Antibiotics, Antitubercular; Antipsychotic Agents; Area Under Curve; Capsules; Chromatography, High Pressure Liquid; Cross-Over Studies; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dizziness; Drug Interactions; Half-Life; Headache; Humans; Male; Nasal Obstruction; Rifampin; Risperidone; Spectrophotometry, Ultraviolet; Tablets; Time Factors

The aim of our study was to evaluate and compare the therapeutic efficacy & safety profile of three different antituberculous regimens for pulmonary tuberculosis. The study sample size included 90 newly diagnosed, sputum positive patients of pulmonary. tuberculosis. 30 each from different groups. The parameters studied were, therapeutic efficacy included weight gain, cough, sputum examination and safety profile: nausea, vomiting, anorexia, gastritis, hepatitis, jaundice diarrhoea, rashes, dizziness, tingling & numbness, flu like symptoms & joint aches. Group-I showed statistically significant weight gain when compared to Group-II. Improvement in cough and conversion to smear negative were seen in 100% of patients in Group-I, 83.3% of patients in Group-II and 93.3% of patients in Group-III. Therapeutic efficacy was highest with Group I regimen, followed by Group III and Group II which was least efficacious. Group II also registered; the maximum cost and highest incidence of adverse effects.

Topics: Adult; Antitubercular Agents; Dizziness; Drug Therapy, Combination; Ethambutol; Female; Follow-Up Studies; Gastritis; Humans; Hypesthesia; Isoniazid; Male; Nausea; Pyrazinamide; Rifampin; Streptomycin; Treatment Outcome; Tuberculosis, Pulmonary

A controlled comparison of 3 short-course regimens was undertaken in patients with newly diagnosed, sputum-positive, pulmonary tuberculosis in South India. The regimens were: R3: rifampin plus streptomycin plus isoniazid plus pyrazinamide daily for 3 months; 5: the same as regimen R3 followed by streptomycin plus isoniazid plus pyrazinamide twice weekly for 2 months; Z5: the same as regimen R5 but without rifampin. The distributions of various pretreatment characteristics were similar in the 3 series. At the end of treatment, 6 patients (3 R3, 3 Z5) of 694 (228 R3, 230 R5, 236 Z5) with drug-sensitive organisms initially were classified as having an unfavorable response. By 24 months (21 months of follow-up for the R3 regimen and 19 months for the R5 and Z5 regimens), a bacteriologic relapse requiring treatment occurred in 20% of 200 R3, 4% of 187 R5, and 13% of 199 Z5 patients, the difference between the R3 and R5 series being highly significant (p = 0.00001). Considering patients with cultures initially resistant to isoniazid, 4 of 57 in the R3 and R5 series combined had an unfavorable response to treatment compared with 13 of 26 in the Z5 series (p less than 0.0001). Of the 4 patients with an unfavorable response in the R3 and R5 series combined, resistance to rifampin emerged in 2. Complaints of arthralgia were made by 45% of the R3 and R5 patients combined and 70% of the Z5 patients (p less than 0.00001). However, chemotherapy was modified in only 5 and 12%, respectively. Jaundice occurred in 7% of the R3 and R5 patients and 1% of the Z5 patients (p less than 0.00001).

Topics: Adolescent; Adult; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Dizziness; Drug Administration Schedule; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; India; Isoniazid; Joint Diseases; Male; Middle Aged; Pyrazinamide; Recurrence; Rifampin; Streptomycin; Time Factors; Tuberculosis, Pulmonary

p-Chloroaniline is more potent at producing methemoglobin than aniline in animal models. This case highlights the clinical presentation of an inhalation exposure to p-chloroaniline and associated laboratory analysis. An in-vitro study evaluating the metabolism of p-chloroaniline in human hepatocytes was undertaken to evaluate the metabolic fate more closely.. A 20 year-old man was working at a chemical waste plant when he developed dizziness, abdominal pain, and nausea. The exam was remarkable for coma, tachycardia, cyanosis, and pulse oximetry of 75%. Arterial blood gases showed a pH 7.38, pCO(2) 41 mmHg, pO(2) 497 mmHg, bicarbonate 24 mEq/L and methemoglobin 69%. Methylene blue administration led to complete recovery without sequelae. p-Chloroaniline was later identified as the chemical involved. He denied direct contact with the chemical, but was not wearing a dust mask or respirator. GC/MS confirmed p-chloroaniline and metabolites in the patient's urine.. Human hepatocytes were incubated with 100 microM p-chloroaniline for 24 hours, in both rifampicin- and vehicle only-treated cells. The cell culture medium was collected for GC/MS analysis for p-chloroaniline metabolites.. Similar to the patient sample, both p-chloroaniline and p-chloroacetanilide were identified by GC/MS in hepatocytes incubated with p-chloroaniline. Neither p-chloroaniline incubated in empty cell culture nor direct GC/MS injection of p-chloroaniline generated any p-chloroacetanilide via non-enzymatic degradation.. The seemingly innocuous dermal and inhalation exposure to p-chloroaniline dust can lead to life-threatening methemoglobinemia. The diagnosis can be confirmed with GC/MS analysis of the patient's urine, searching for p-chloroaniline and its primary metabolite p-chloroacetanilide.

Topics: Abdominal Pain; Acetanilides; Air Pollutants; Aniline Compounds; Antidotes; Bicarbonates; Cells, Cultured; Clinical Laboratory Techniques; Coma; Cyanosis; Dizziness; Gas Chromatography-Mass Spectrometry; Hepatocytes; Humans; Inhalation Exposure; Male; Methemoglobin; Methemoglobinemia; Methylene Blue; Nausea; Occupational Exposure; Oximetry; Rifampin; Tachycardia; Toxicology; Young Adult

Two cases of 'flu' syndrome on once monthly rifampicin are reported. The symptoms were reproduced in one patient with the next supervised dose. In the second patient they did not recur probably because she was receiving systemic steroids for left ulnar neuritis.

Topics: Adult; Dizziness; Drug Administration Schedule; Female; Fever; Humans; Leprosy, Borderline; Rifampin; Shivering; Syndrome