Rifampicin in opioid-induced itching

Pruritus is prevalent in 5-12% of palliative care patients. Rifampicin has been shown to be useful both as initial treatment and as salvage treatment after failure of other agents to control the pruritus associated with the cholestatic jaundice of malignancy. We report the case of a 65-year-old woman who complained of severe pruritus after morphine treatment. The use of rifampicin 300 mg twice a day by the i.v. route was successful, and after opioid switching it was no longer necessary to maintain rifampicin in the therapeutic regimen. Controlled clinical trials are warranted to confirm this preliminary observation.     

Rifampicin pharmacokinetics with and without ciprofloxacin

We investigated the effect of ciprofloxacin on rifampicin pharmacokinetics in five healthy subjects. Each subject received 600 mg rifampicin with 350 mL of water, and in the second phase, each subject received 600 mg rifampicin plus 500 mg ciprofloxacin with 350 mL of water. In each of the two phases, plasma rifampicin levels were measured from 1 to 24 hours. Treatment with ciprofloxacin significantly increased the half-life and also significantly decreased the maximum peak concentration of rifampicin. Area under the curve time for peak plasma concentration and volume of distribution were not significantly affected. In this study, we found that ciprofloxacin increases the half-life and reduces the maximum concentration of rifampicin in humans.     

Effect of Gemfibrozil,Rifampicin, or Probenecid on the Pharmacokinetics of the SGLT2 Inhibitor Empagliflozin in Healthy Volunteers

Background

Empagliflozin is a potent, oral, selective inhibitor of sodium glucose cotransporter 2 in development for the treatment of type 2 diabetes mellitus.

Objective

The goal of these studies was to investigate potential drug–drug interactions between empagliflozin and gemfibrozil (an organic anion-transporting polypeptide 1B1 [OATP1B1]/1B3 and organic anion transporter 3 [OAT3] inhibitor), rifampicin (an OATP1B1/1B3 inhibitor), or probenecid (an OAT3 and uridine diphosphate glucuronosyltransferase inhibitor).

Methods

Two open-label, randomized, crossover studies were undertaken in healthy subjects. In the first study, 18 subjects received the following in 1 of 2 randomized treatment sequences: a single dose of empagliflozin 25 mg alone and gemfibrozil 600 mg BID for 5 days with a single dose of empagliflozin 25 mg on the third day. In the second study, 18 subjects received a single dose of empagliflozin 10 mg, a single dose of empagliflozin 10 mg coadministered with a single dose of rifampicin 600 mg, and probenecid 500 mg BID for 4 days with a single dose of empagliflozin 10 mg on the second day in 1 of 6 randomized treatment sequences.

Results

In the gemfibrozil study, 11 subjects were male, mean age was 35.1 years and mean body mass index (BMI) was 23.47 kg/m². In the rifampicin/probenecid study, 10 subjects were male, mean age was 32.7 years and mean BMI was 23.03 kg/m². Exposure to empagliflozin was increased by coadministration with gemfibrozil (AUC_0–∞: geometric mean ratio [GMR], 158.50% [90% CI, 151.77–165.53]; C_max: GMR, 115.00% [90% CI, 106.15–124.59]), rifampicin (AUC_0–∞: GMR, 135.20% [90% CI, 129.58–141.06]; C_max: GMR, 175.14% [90% CI, 160.14–191.56]), and probenecid (AUC_0–∞: GMR, 153.47% [90% CI, 146.41–160.88]; C_max: GMR, 125.60% [90% CI, 113.67–138.78]). All treatments were well tolerated.

Conclusions

Increases in empagliflozin exposure were <2-fold, indicating that the inhibition of the OATP1B1/1B3, OAT3 transporter, and uridine diphosphate glucuronosyltransferases did not have a clinically relevant effect on empagliflozin exposure. No dose adjustments of empagliflozin were necessary when it was coadministered with gemfibrozil, rifampicin, or probenecid. ClinicalTrials.gov identifiers: NCT01301742 and NCT01634100.     

Rifampicin for non-tuberculous infections?

Large populations of rifampicin-sensitive strains of Mycobacterium tuberculosis have been exposed in vitro to changing concentrations of rifampicin (RIF) in line with changes in the blood level of the drug observed during treatment, and to much lower concentrations. Experiments in which the organism was exposed to either 7 or 14 days of cyclically-changing rifampicin concentrations have resulted in the elimination of the M. tuberculosis test strains without the emergence of RIF resistance. The significance of these laboratory findings is discussed in relation to the debate as to whether rifampicin should be used in short courses for the treatment of non-tuberculous infections or whether it should be withheld for fear of inadvertently generating rifampicin-resistant strains of tubercle bacilli. It is argued that the evidence for withholding rifampicin from use in short courses against non-tuberculous infections is slight.     

Rifampicin resistance and its fitness cost in Enterococcus faecium

OBJECTIVES: The genetic basis of rifampicin resistance and the associated fitness cost in Enterococcus faecium were investigated. METHODS: Twelve spontaneous rifampicin-resistant E. faecium mutants were selected from four parent strains recently isolated from porcine faecal material. The DNA sequence of the complete rpoB gene from the parent strains and of nucleotides -189 to +1785 from the mutants was determined from PCR amplicons. The fitness of the mutants was assessed by determining growth rate, by direct growth competition and by the ability of some of the mutants to survive in the pig intestine. RESULTS: The rpoB genes of the parent strains diverged from each other by 1-10% and each encoded proteins that were 1208 amino acids in length. All mutants had a single amino acid substitution in the region implicated in rifampicin resistance in other organisms. Six mutants carried the substitution H489Y/Q, two mutants carried the substitution R492H, one mutant carried the substitution Q480H, two mutants carried the substitutions S494L and V224I, and one mutant carried the substitutions G485D and V224I. Per generation fitness costs of the mutants ranged from a gain of 2.5% to a cost of 10%. Mutants with the substitution H489Y/Q were the most fit, whereas the double mutants were the least fit. The mutant with the substitution H489Q was able to survive in the pig gut for 12 days. There was some correlation between the rifampicin MIC and fitness cost, with higher MICs being associated with higher fitness costs. CONCLUSIONS: Substitutions in RpoB are associated with rifampicin resistance in E. faecium. The fitness cost of resistance is variable and can sometimes be absent.     

影响回路内麻醉气体吸附器效果多因素分析

目的：研究XF—9801型活性炭吸附器对异氟醚吸入麻醉的吸附效果的影响因素。方法：20例择期手术病人,术中根据手术需要调整蒸发器刻度维持异氟醚呼气末浓度0.6～1.0MAC,记录病人的麻醉持续时间和呼气末异氟醚浓度,手术结束,使用回路内吸附器后,达到呼气末异氟醚浓度0.2%和0.3%所持续的时间,将该时间与麻醉持续时间、呼气末异氟醚浓度、体重、年龄进行逐步回归分析。结果：回路内吸附器使用后,达到呼气末异氟醚浓度0.2%和0.3%所持续的时间分别为8.0±2.3min和2.5±1.2min,而且该时间与呼气末异氟醚浓度、体重、麻醉持续时间和年龄呈现明显的相关性(P＜0.05)。病人的苏醒时间为12.3±4.5min。结论：回路内吸附器使用后,呼气末异氟醚浓度0.2%和0.3%所持续的时间分别与呼气末异氟醚浓度、体重、麻醉持续时间和年龄呈现明显的相关性。使用回路内活性炭吸附器后病人的苏醒时间明显缩短。     

Long-Term Hemoperfusion with Coated Activated Charcoal

Abstract

Sulfasalazine (salicylazosulfapyridine, Azulfidine) has been widely used over the last half century for inflammatory bowel diseases, but overdose has not been reported. A 23 year-old male ingested 25?g of sulfasalazine in a suicide attempt. He underwent prompt treatment and survived with no ill-effects.     

Rifampicin against experimental listeriosis in the mouse.

The activity of rifampicin was compared with that of tetracycline, ampicillin, penicillin G, chloramphenicol, gentamicin and sulphadiazine in vitro and in experiments on mice infected with various strains of Listeria monocytogenes. Although the minimum inhibitory concentration of rifampicin was not appreciably lower than that of ampicillin, penicillin G and gentamicin, rifampacin was very much more active in vivo than any of these antibiotics. One of the reasons for its greater efficacy may be that it inhibits or destroys intracellular Listeria. In addition, a synergistic effect was observed in vivo when rifampicin was administered in combination with ampicillin or tetracyline. The combined administration of rifampicin with either of these antibiotics should prevent the emergence of rifampicin-resistant Listeria.     

Position Paper: Single-Dose Activated Charcoal

Single-dose activated charcoal therapy involves the oral administration or instillation by nasogastric tube of an aqueous preparation of activated charcoal after the ingestion of a poison. Volunteer studies demonstrate that the effectiveness of activated charcoal decreases with time. Data using at least 50 g of activated charcoal, showed a mean reduction in absorption of 47.3%, 40.07%, 16.5% and 21.13%, when activated charcoal was administered at 30 minutes, 60 minutes, 120 minutes and 180 minutes, respectively, after dosing. There are no satisfactorily designed clinical studies assessing benefit from single-dose activated charcoal to guide the use of this therapy.

Single-dose activated charcoal should not be administered routinely in the management of poisoned patients. Based on volunteer studies, the administration of activated charcoal may be considered if a patient has ingested a potentially toxic amount of a poison (which is known to be adsorbed to charcoal) up to one hour previously. Although volunteer studies demonstrate that the reduction of drug absorption decreases to values of questionable clinical importance when charcoal is administered at times greater than one hour, the potential for benefit after one hour cannot be excluded. There is no evidence that the administration of activated charcoal improves clinical outcome. Unless a patient has an intact or protected airway, the administration of charcoal is contraindicated. A review of the literature since the preparation of the 1997 Single-dose Activated Charcoal Position Statement revealed no new evidence that would require a revision of the conclusions of the Statement.     

Rifampicin reverses nicardipine effect inducing uncontrolled essential hypertension

Dihydropyridine calcium‐channel blockers are a known substrate for the cytochrome P450 isoform 3A4. Rifampicin, an antitubercular agent, is one of the most potent inducers of hepatic and intestinal CYP3A4 thus increasing dihydropyridine metabolism. We report a case of a 67‐year‐old hypertensive female treated with a four‐drug antihypertensive regimen including a dihydropyridine (nicardipine 50 mg bid), who was admitted for septic arthritis of the knee requiring antibiotic treatment with teicoplanin 400 mg od and rifampicin 600 mg bid. Six days after rifampicin initiation, she presented with Posterior Reversible Encephalopathy Syndrome due to uncontrolled hypertension. We hypothesized that disequilibrium of previously controlled hypertension was partially due to nicardipine ineffectiveness. Plasma nicardipine concentration was assessed through high‐performance liquid chromatography 5 hours after coadministration of the two drugs and proved undetectable.     

Rifampicin test in the diagnosis of Gilbert's syndrome

Gilbert's syndrome (GS) is characterised by the existence of chronic mild unconjugated hyperbilirubinaemia. The value of rifampicin as a provocative test for the diagnosis of GS was evaluated and compared with a fasting test. Twenty-two patients with GS, 15 patients with chronic liver disease and 20 healthy controls were included. Both rifampicin and fasting tests were applied to all subjects. In the fasting test, the subjects were given a 400 calorie/day diet for 24 hours; in the rifampicin test, unconjugated bilirubin levels was measured before and four hours after taking 600 mg of rifampicin. Both tests achieved a significant increase in mean unconjugated bilirubin levels in patients with GS but not in the controls. The sensitivity and specificity of a rifampicin test in the diagnosis of GS were comparable with the fasting test. However, both tests caused a significant increase in unconjugated bilirubin levels in nearly half the patients with chronic liver disease. A rifampicin test may be used in the diagnosis of suspected GS instead of a fasting test, as it is simpler and more practical. However, its specificity for GS is not sufficient, because it also causes an increase in unconjugated bilirubin levels in some patients with chronic liver disease.