Pharmacokinetics of rifampicin in Mexican patients with tuberculosis and healthy volunteers

Medellín‐Garibay, Susanna Edith; Milán‐Segovia, Rosa del Carmen; Magaña-Aquino, Martín; Portales-Pérez, Diana Patricia; Romano‐Moreno, Silvia

doi:10.1111/jphp.12275

Cited by 14 publications

(17 citation statements)

References 29 publications

(41 reference statements)

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“…Rifampicin CL/F and V/F estimated parameters were in line with those previously reported in patients treated for tuberculosis [14,25,26,28]. Moreover, these parameters were highly variable and confirmed the wide interindividual pharmacokinetic variability of rifampicin [14,15].…”

Section: Discussionsupporting

confidence: 89%

“…However, in our study the addition of a second transit compartment did not lead to a better estimation of parameters, probably due to insufficient blood sampling prior to the attainment of the maximum postdose concentration. A model with one transit compartment resulted in a structural model presenting a lower OFV compared with a model with an absorption lag‐time parameter, as reported in a previous study . Indeed, the lag‐time parameter, which reproduces an instantaneous shift from no absorption to maximal absorption, is physiologically implausible and associated with computational difficulties.…”

Section: Discussionmentioning

confidence: 64%

See 1 more Smart Citation

Population pharmacokinetics of rifampicin in adult patients with osteoarticular infections: interaction with fusidic acid

Marsot

Ménard

Dupouey

et al. 2017

Brit J Clinical Pharma

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 64%

Population pharmacokinetics of rifampicin in adult patients with osteoarticular infections: interaction with fusidic acid

Marsot

Ménard

Dupouey

et al. 2017

Brit J Clinical Pharma

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“…In addition, drug exposures based on the administration of weight‐adjusted doses recommended by the WHO were explored. Plasma concentrations of RIF, PZA and INH were described by one‐compartment, one‐compartment and two‐compartment models, respectively, which were consistent with the models used in previous studies 15,20–28 . Our population models identified significant effects of weight on PK parameters of RIF, INH and PZA.…”

Section: Discussionsupporting

confidence: 84%

Drug exposure of first‐line anti‐tuberculosis drugs in China: A prospective pharmacological cohort study

Forsman

Ren

Zheng

et al. 2020

Brit J Clinical Pharma

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Aim Exploring the need for optimization of drug exposure to improve tuberculosis (TB) treatment outcome is of great importance. We aimed to describe drug exposure at steady state as well as the population pharmacokinetics (PK) of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) in Chinese TB patients. Methods A prospective multicentre PK study of RIF, INH and PZA was conducted in China between January 2015 and December 2017. Six blood samples were collected from each subject for drug concentration measurement. Nonlinear mixed effect analyses were used to develop population PK models. Results In total, 217 patients were included. Positive correlations between body weight, clearance and volume of distribution were identified for RIF and PZA, whereas body weight only influenced clearance for INH. In addition, males had higher RIF clearance and thus lower RIF exposure than women. Acetylator status was significantly associated with INH clearance as INH exposure in intermediate and fast acetylators was significantly lower than in slow acetylators, especially in low‐weight bands. Simulations also showed significantly lower drug exposures in low‐weight bands for all three drugs. Patients weighing <38 kg were respectively exposed to 30.4%, 45.9% and 18.0% lower area under the concentration‐time curve of RIF, INH and PZA than those weighing ≥70 kg. Higher doses by addition of one fixed‐dose combination tablet or 150 mg INH were simulated and found to be effective in improving INH drug exposures, especially in low‐weight bands. Conclusion PK variability of first‐line anti‐TB drugs is common in Chinese TB patients. The developed population PK models can be used to optimize drug exposures in Chinese patients. Moreover, standard dosing needs to be adjusted to increase target attainment.

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“…Indeed, the phenotype of Cyp27a1 KO mice was mainly expressed in the liver, with a severe microvesicular steatosis, whereas CYP27A1 deficiency in humans with Cerebrotendinous Xanthomatosis (CTX), clinical manifestations include bilateral juvenile cataracts and accumulation of cholestanol in different tissues [ 21 ]. For many years, RIF was used as an antibiotic for the treatment of tuberculosis and it is still used in clinical practice [ 12 ]. CTX, patients, induction of CYP3A4 activity by RIF cannot replace the effective therapy with chenodeoxycholic acid (CDCA).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, pharmacodynamic approaches modulating CYP3A4 activity offers an attractive option to target therapeutic effects of endo- or xenobiotics metabolized by CYP3A4 in humans. Rifampicin (RIF), often administered as an antibiotic for the treatment of tuberculosis, is a potent CYP3A4 inducer [ 12 ]. It exerts its activity via Pregnane X receptor (PXR) activation [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Sterol 27-hydroxylase gene dosage and the antiatherosclerotic effect of Rifampicin in mice

et al. 2018

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Sterol 27-hydroxylase (CYP27A1) catalyzes the hydroxylation of cholesterol to 27-hydroxycholesterol (27-OHC) and regulates cholesterol homeostasis. In Cyp27a1/ Apolipoprotein E (ApoE) double knockout (KO) mice fed with Western diet (WD), the atherosclerotic phenotype found in ApoE KO mice was reversed. As protective mechanism, up-regulation of Cyp3a11 and Cyp7a1 was proposed. Cyp27a1 heterozygote/ApoE KO (het) mice, with reduced Cyp27a1 expression and normal levels of Cyp7a1 and Cyp3a11, developed more severe lesions than ApoE KO mice. To analyze the contribution of Cyp3a11 to the protection of atherosclerosis development, Cyp3a11 was induced by Rifampicin (RIF) in ApoE KO and het mice. Males were fed with WD and treated daily with RIF (10 mg/kg ip) or vehicle for 4 weeks. Atherosclerosis was quantified in the aortic valve. Plasma lipids and 27-hydroxycholesterol (27-OHC), expression of cytochromes P450 and genes involved in cholesterol transport and bile acids (BAs) signaling in liver and intestine, and intestinal cholesterol absorption were analyzed. RIF increased expression of hepatic but not intestinal Cyp3a11 4-fold in both genotypes. In ApoE KO mice treated with RIF, we found a 2-fold decrease in plasma cholesterol, and a 2-fold increase in high-density lipoprotein/low-density lipoprotein ratio and CY27A1 activity. Intestinal cholesterol absorption remained unchanged and atherosclerotic lesions decreased approximately 3-fold. In het mice, RIF had no effect on plasma lipids composition, CYP27A1 activity, and atherosclerotic plaque development, despite a reduction in cholesterol absorption. In conclusion, the antiatherogenic effect of Cyp3a11 induction by RIF was also dependent on Cyp27a1 expression.

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Pharmacokinetics of rifampicin in Mexican patients with tuberculosis and healthy volunteers

Abstract: The main differences in PK parameters of RIF between Mexican TB patients and healthy volunteers were demonstrated in absorption and distribution processes. In addition, differences in PK parameters observed by sex should be considered for further dosing recommendations.

Cited by 14 publications

References 29 publications

Population pharmacokinetics of rifampicin in adult patients with osteoarticular infections: interaction with fusidic acid

Population pharmacokinetics of rifampicin in adult patients with osteoarticular infections: interaction with fusidic acid

Drug exposure of first‐line anti‐tuberculosis drugs in China: A prospective pharmacological cohort study

Sterol 27-hydroxylase gene dosage and the antiatherosclerotic effect of Rifampicin in mice

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