Dapsone and Body Mass Index in Subjects With Multibacillary Leprosy

Moura, Fernanda Maria Lima; Dias, Rosa Mª Donini Souza; Araujo, Eliete C.; Brasil, Laélia Maria Barra Feio; Ferreira, Michelle Valéria Dias; Vieira, José Luiz Fernandes

doi:10.1097/ftd.0b013e3182a8f0c8

Cited by 7 publications

(9 citation statements)

References 17 publications

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“…According to data from the Brazilian Household Budget Survey (2010) on nutritional status, the prevalence of overweight and obesity is high in Brazil, affecting half the adult population [19]. Similar results have been reported in other studies [16, 29]. In contrast, a high degree of malnutrition has been observed in studies conducted in India (BMI < 17 kg/m 2 ) [30, 31].…”

Section: Discussionsupporting

confidence: 64%

Correlation between therapy and lipid profile of leprosy patients: is there a higher risk for developing cardiovascular diseases after treatment?

et al. 2017

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BackgroundThe impact of leprosy reduces health-related quality of life of affected patients, interfering with different factors such as nutrition. This study investigated the lipid profile, nutritional status, and risk for cardiovascular disease (CVD) in patients who underwent leprosy treatment in Brazil.MethodsEighty-four adult patients of both genders ranging in age from 20 to 60 years and diagnosed with paucibacillary (PB) or multibacillary (MB) leprosy were selected after undergoing multidrug treatment. The following data were collected: sociodemographic and clinical data; food intake; anthropometric measures (weight, height, and waist circumference); and lipid profile components (total cholesterol, high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], and triglycerides).ResultsAmong the study population, there was a predominance of males (65.48%) aged 50 to 60 years, patients with an income of 248–496 American dollars (63.10%), patients who completed elementary school (65.48%), inactive patients (76.19%), non-smokers (46.43%), and non-drinking patients (69.05%). The levels (mean ± standard deviation) of total cholesterol were 193.8 ± 29.4 mg/dL in the PB form and 203.5 ± 41.7 mg/dL in the MB form. The mean LDL-c was 116.9 ± 22.7 mg/dL in PB patients and 121 ± 31.3 mg/dL in MB patients. Mean triglyceride levels were 123.4 ± 45.2 mg/dL in the PB form and 147.4 ± 88.9 mg/dL in the MB form. The evaluation of nutritional status showed that 41.67% of the patients were eutrophic, while 55.96% had excess weight. Food intake was significantly associated with HDL-c in male patients (P = 0.0264) and with triglycerides in patients above the ideal weight (P = 0.0049).ConclusionsThe risk of acquiring CVDs was observed to be high due to patients’ excess weight and increased waist circumference. This study will guide clinicians in the adequate treatment of patients with leprosy in order to avoid adverse cardiovascular events.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-017-0295-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 64%

Correlation between therapy and lipid profile of leprosy patients: is there a higher risk for developing cardiovascular diseases after treatment?

et al. 2017

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“…The pharmacokinetic parameters of dapsone could be altered by the disease process it is administered to treat, by disease severity, and at steady state. However, the pharmacokinetic parameter estimates in our base model are similar to those observed by other investigators using multiple doses and/or evaluating patients with active disease . We also did not evaluate routes of disposition or the effect of dapsone metabolites, so that we did not evaluate the physiological reasons why obese patients have higher drug metabolism.…”

Section: Discussionmentioning

confidence: 67%

“…Overweight is a BMI ≥25 kg/m 2 and obesity a BMI ≥30 kg/m 2 . In the case of dapsone, the impact of weight on drug concentrations has been assumed to be linear through all ranges, such that both systemic clearance and volume of distribution have been considered to increase linearly for each 1 kg increase above body mass (colloquial term “weight”), not BMI . However, based on some of our prior studies, such linear relationships in biologic systems over a wide range of values should be suspect .…”

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confidence: 99%

“…Moreover, the effect of weight on pharmacokinetics in the ranges of up to 150 kg, now increasingly encountered in patients, has hitherto not been investigated for dapsone. Prior studies have been of relatively underweight patients and mixtures of babies and adults . Here, we optimized a clinical experimental study design to more precisely identify the effects of obesity on dapsone pharmacokinetic parameters.…”

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confidence: 99%

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Supervised Machine-Learning Reveals That Old and Obese People Achieve Low Dapsone Concentrations

Hall

Pasipanodya

Swancutt

et al. 2017

CPT Pharmacometrics Syst. Pharmacol.

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The human species is becoming increasingly obese. Dapsone, which is extensively used across the globe for dermatological disorders, arachnid bites, and for treatment of several bacterial, fungal, and parasitic diseases, could be affected by obesity. We performed a clinical experiment, using optimal design, in volunteers weighing 44–150 kg, to identify the effect of obesity on dapsone pharmacokinetic parameters based on maximum‐likelihood solution via the expectation‐maximization algorithm. Artificial intelligence‐based multivariate adaptive regression splines were used for covariate selection, and identified weight and/or age as predictors of absorption, systemic clearance, and volume of distribution. These relationships occurred only between certain patient weight and age ranges, delimited by multiple hinges and regions of discontinuity, not identified by standard pharmacometric approaches. Older and obese people have lower drug concentrations after standard dosing, but with complex patterns. Given that efficacy is concentration‐dependent, optimal dapsone doses need to be personalized for obese patients.

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“…Nevertheless, dose adjustments might be needed for obese patients treated with this regimen [59]. Various drug–drug interaction studies did not reveal clinical significant interactions, although little is known about the required minimal effective exposure in leprosy [61–64].…”

Section: Resultsmentioning

confidence: 99%

Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review

Verrest

Dorlo

2016

Clin Pharmacokinet

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IntroductionNeglected tropical diseases (NTDs) affect more than one billion people, mainly living in developing countries. For most of these NTDs, treatment is suboptimal. To optimize treatment regimens, clinical pharmacokinetic studies are required where they have not been previously conducted to enable the use of pharmacometric modeling and simulation techniques in their application, which can provide substantial advantages.ObjectivesOur aim was to provide a systematic overview and summary of all clinical pharmacokinetic studies in NTDs and to assess the use of pharmacometrics in these studies, as well as to identify which of the NTDs or which treatments have not been sufficiently studied.MethodsPubMed was systematically searched for all clinical trials and case reports until the end of 2015 that described the pharmacokinetics of a drug in the context of treating any of the NTDs in patients or healthy volunteers.ResultsEighty-two pharmacokinetic studies were identified. Most studies included small patient numbers (only five studies included >50 subjects) and only nine (11 %) studies included pediatric patients. A large part of the studies was not very recent; 56 % of studies were published before 2000. Most studies applied non-compartmental analysis methods for pharmacokinetic analysis (62 %). Twelve studies used population-based compartmental analysis (15 %) and eight (10 %) additionally performed simulations or extrapolation. For ten out of the 17 NTDs, none or only very few pharmacokinetic studies could be identified.ConclusionsFor most NTDs, adequate pharmacokinetic studies are lacking and population-based modeling and simulation techniques have not generally been applied. Pharmacokinetic clinical trials that enable population pharmacokinetic modeling are needed to make better use of the available data. Simulation-based studies should be employed to enable the design of improved dosing regimens and more optimally use the limited resources to effectively provide therapy in this neglected area.Electronic supplementary materialThe online version of this article (doi:10.1007/s40262-016-0467-3) contains supplementary material, which is available to authorized users.

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Dapsone and Body Mass Index in Subjects With Multibacillary Leprosy

Abstract: Obesity promotes a significant reduction in plasma dapsone trough levels of subjects with multibacillary leprosy with a weak association between drug levels and BMI.

Cited by 7 publications

References 17 publications

Correlation between therapy and lipid profile of leprosy patients: is there a higher risk for developing cardiovascular diseases after treatment?

Correlation between therapy and lipid profile of leprosy patients: is there a higher risk for developing cardiovascular diseases after treatment?

Supervised Machine-Learning Reveals That Old and Obese People Achieve Low Dapsone Concentrations

Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review

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