Intestinal barrier function and serum concentrations of rifampin, isoniazid and pyrazinamide in patients with pulmonary tuberculosis

Façanha, Mônica Cardoso; Gondim, A.; Pinheiro, Valéria Goes Ferreira; E, Barroso; Peloquin, Charles A.; Guerrant, Richard L.; Lima, Aldo A. M.

doi:10.1590/s1413-86702009000300011

Cited by 11 publications

(11 citation statements)

References 26 publications

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“…In this study, it was possible to detect patients and healthy volunteers who showed a suboptimal level of RIF. These data match with those in other studies performed in TB patients with or without HIV or type II diabetes mellitus [8,9,19]…”

Section: Discussionsupporting

confidence: 91%

“…It was interesting to identify a process of latency in the absorption of RIF in most of the pharmacokinetic profiles, which ranged from 20 min to 1.4 h. Only two healthy volunteers and one TB patient did not show this tlag. This drug belongs to Class II (low solubility–high permeability) of the Biopharmaceutical Classification System and then tlag may be affected by such characteristics,[24–26] resulting in delayed absorption as well as significant variations in bioavailability [9,16]…”

Section: Discussionmentioning

confidence: 99%

“…The activity of RIF against Mycobacterium tuberculosis is concentration dependent, and some reports suggest that the apparition of resistant isolates in previously treated cases are associated with low plasma concentrations caused by delayed drug absorption or poor bioavailability of the formulation [7–11]. Previous studies evaluated the pharmacokinetics (PK) of RIF in healthy volunteers or patients with TB, and in the latter, generally performed multiple dose studies to obtain plasma levels in the steady state.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of rifampicin in Mexican patients with tuberculosis and healthy volunteers

Medellín‐Garibay

Milán‐Segovia

Magaña-Aquino

et al. 2014

Journal of Pharmacy and Pharmacology

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of rifampicin in Mexican patients with tuberculosis and healthy volunteers

Medellín‐Garibay

Milán‐Segovia

Magaña-Aquino

et al. 2014

Journal of Pharmacy and Pharmacology

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“…HIV is known to target the small intestine, especially the gutassociated lymphoid tissue, and HIV-mediated enteropathy is associated with malabsorption (27). Decrease in the functional absorptive area of the intestine has been associated with reduced TB drug availability (28)(29)(30)(31). The recovery mechanism whereby nutritional supplementation may restore the pathophysiology and immunological changes is not explained and warrants further studies (26).…”

Section: Discussionmentioning

confidence: 99%

Nutritional Supplementation Increases Rifampin Exposure among Tuberculosis Patients Coinfected with HIV

Jeremiah

Denti

Cosson

et al. 2014

Antimicrob Agents Chemother

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f Nutritional supplementation to tuberculosis (TB) patients has been associated with increased weight and reduced mortality, but its effect on the pharmacokinetics of first-line anti-TB drugs is unknown. 2 ) were randomized to receive nutritional supplementation during the intensive phase of TB treatment. Rifampin plasma concentrations were determined after 1 week and 2 months of treatment. The effects of nutritional supplementation, HIV, time on treatment, body weight, and SLCO1B1 rs4149032 genotype were examined using a population pharmacokinetic model. The model adjusted for body size via allometric scaling, accounted for clearance autoinduction, and detected an increase in bioavailability (؉14%) for the patients in the continuation phase. HIV coinfection in patients not receiving the supplementation was found to decrease bioavailability by 21.8%, with a median maximum concentration of drug in serum (C max ) and area under the concentration-time curve from 0 to 24 h (AUC 0 -24 ) of 5.6 g/ml and 28.6 g · h/ml, respectively. HIV-coinfected patients on nutritional supplementation achieved higher C max and AUC 0 -24 values of 6.4 g/ml and 31.6 g · h/ml, respectively, and only 13.3% bioavailability reduction. No effect of the SLCO1B1 rs4149032 genotype was observed. In conclusion, nutritional supplementation during the first 2 months of TB treatment reduces the decrease in rifampin exposure observed in HIV-coinfected patients but does not affect exposure in HIV-uninfected patients. If confirmed in other studies, the use of defined nutritional supplementation in HIV-coinfected TB patients should be considered in TB control programs. (This study has the controlled trial registration number ISRCTN 16552219.)

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“…HIV is a common co-infection in patients presenting with tuberculosis. Several studies have investigated the association of HIV infection with the pharmacokinetics of the first-line drugs for DS-TB [2,21,[62][63][64][65]. The findings across different studies are not consistent.…”

Section: Other Clinical Characteristicsmentioning

confidence: 99%

Current research toward optimizing dosing of first-line antituberculosis treatment

McIlleron

Chirehwa

2018

Expert Review of Anti-infective Therapy

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Introduction: Drug concentrations in tuberculosis patients on standard regimens vary widely with clinically important consequences.Areas covered: We review the available literature identifying factors correlated with pharmacokinetic variability of antituberculosis drugs. Based on population pharmacokinetic models and the weight, height, and sex distributions in a large data base of African tuberculosis patients, we propose simplified weight-based doses of the available fixed dose combination(FDC) for adults with drug susceptible tuberculosis. Emerging studies will support optimized weight-based dosing for children. Other sources of important pharmacokinetic variability include genetic variants, drug-drug interactions, formulation quality, and methods of preparation and administration.Expert commentary: Optimized weight band-based dosing will result in more equitable distribution of drug exposures by weight. The use of high doses of isoniazid in patients with drug-resistant tuberculosis would be safer and more effective if a feasible test was developed to allow stratified dosing according to acetylator type. There is an urgent need for more suitable formulations of many second-line drugs for children. The adoption of new technologies and efficient FDC design may allow further advances for patients and treatment programs. Lastly, current efforts to ensure adequate quality of antituberculosis drug products are not preventing the use of substandard products to treat patients with tuberculosis.

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Intestinal barrier function and serum concentrations of rifampin, isoniazid and pyrazinamide in patients with pulmonary tuberculosis

Cited by 11 publications

References 26 publications

Pharmacokinetics of rifampicin in Mexican patients with tuberculosis and healthy volunteers

Pharmacokinetics of rifampicin in Mexican patients with tuberculosis and healthy volunteers

Nutritional Supplementation Increases Rifampin Exposure among Tuberculosis Patients Coinfected with HIV

Current research toward optimizing dosing of first-line antituberculosis treatment

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