Limited-Sampling Strategies for Anti-Infective Agents: Systematic Review

Sprague, Denise A; Ensom, Mary H H

doi:10.4212/cjhp.v62i5.827

Cited by 6 publications

(4 citation statements)

References 42 publications

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“…The results might be useful for designing a limited-sampling strategy in which accurate information on the antiplatelet effect of clopidogrel can be obtained using plasma concentrations determined in a few blood samples at appropriate times. Strategies using a limited number of samples have proven to be useful in therapeutic monitoring of immunosuppressants [ 37 ] or anti-infective agents [ 38 ]. A significant correlation between the pharmacokinetic parameters of clopidogrel and the AUC t of the H4 isomer allows for prediction of patient exposure to the active metabolite in situations when only analysis of the parent compound is available.…”

Section: Discussionmentioning

confidence: 99%

Clinical Pharmacokinetics of Clopidogrel and Its Metabolites in Patients with Cardiovascular Diseases

et al. 2013

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Background and ObjectiveApproximately 5–40 % of patients treated with clopidogrel do not display an adequate antiplatelet response. Clopidogrel resistance may be caused by insufficient drug absorption or impaired metabolic activation of the drug. The aim of this study was to evaluate the pharmacokinetics of clopidogrel and its metabolites in plasma samples from patients treated with high and low doses of clopidogrel, to obtain a possible explanation for antiplatelet resistance.MethodsThe study included patients receiving either a single 300 mg loading dose of clopidogrel (n = 17) or a 75 mg dose (n = 45) for at least 7 days before sample collection. The concentrations of clopidogrel and its metabolites—the inactive H3 and the pharmacologically active H4 isomers of the thiol metabolite and the inactive carboxylic acid metabolite—in plasma samples (stabilized with 2-bromo-3′-methoxyacetophenone) from three patients after 300 mg and from 41 patients after 75 mg of the drug were determined using a validated high-performance liquid chromatography method with tandem mass spectrometry. The non-stabilized samples from the remaining patients were analysed using a validated capillary electrophoresis method. The calculated concentrations were used to determine the pharmacokinetic parameters of the analytes. The pharmacodynamic response to clopidogrel treatment, expressed as adenosine diphosphate-induced platelet aggregation, was measured using a Multiplate analyser.ResultsThe pharmacokinetic parameter values for the H3 and H4 isomers determined in the studied group of patients treated with clopidogrel 75 mg (maximum plasma concentration [Cmax] 5.29 ± 5.54 and 7.13 ± 6.32 ng/mL for H3 and H4, respectively; area under the plasma concentration-time curve from time zero to time t [AUCt] 7.37 ± 6.71 and 11.30 ± 9.58 ng·h/mL for H3 and H4, respectively) were lower than those reported in healthy volunteers, according to the literature data. Platelet aggregation measured with a Multiplate analyser ranged between 37 and 747 AU·min. A significant correlation was found between the Cmax of the active H4 isomer and platelet aggregation (p = 0.025).ConclusionThe Cmax of the active H4 isomer and platelet aggregation measured by the Multiplate analyser may serve as markers of the patient response to clopidogrel therapy.

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Section: Discussionmentioning

confidence: 99%

Clinical Pharmacokinetics of Clopidogrel and Its Metabolites in Patients with Cardiovascular Diseases

et al. 2013

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“…Since only limited samples are available during TDM, the estimation of LVX AUC can be a challenge. One approach to estimate the AUC is to use a well-designed, limited sampling strategy (LSS) (25,26).…”

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Limited Sampling Strategy and Target Attainment Analysis for Levofloxacin in Patients with Tuberculosis

Alsultan

Peloquin

2015

Antimicrob Agents Chemother

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There is an urgent need to improve and shorten the treatment of tuberculosis (TB) and multidrug resistant tuberculosis (MDR-TB). Levofloxacin, a newer fluoroquinolone, has potent activity against TB both in vitro and in vivo. Levofloxacin dosing can be optimized to improve the treatment of both TB and MDR-TB. Levofloxacin efficacy is linked primarily to the ratio of the area under the concentration-time curve for the free fraction of drug (fAUC) to the MIC. Since obtaining a full-time concentration profile is not feasible in the clinic, we developed a limited sampling strategy (LSS) to estimate the AUC. We also utilized Monte Carlo simulations to evaluate the dosing of levofloxacin. Pharmacokinetic data were obtained from 10 Brazilian TB patients. The pharmacokinetic data were fitted with a one-compartment model. LSSs were developed using two methods: linear regression and Bayesian approaches. Several LSSs predicted levofloxacin AUC with good accuracy and precision. The most accurate were the method using two samples collected at 4 and 6 h (R 2 ‫؍‬ 0.91 using linear regression and 0.97 using Bayesian approaches) and that using samples collected at 2 and 6 h (R 2 ‫؍‬ 0.90 using linear regression and 0.96 using Bayesian approaches). The 2-and-6-h approach also provides a good estimate of the maximum concentration of the drug in serum (C max ). Our target attainment analysis showed that higher doses (17 to 20 mg/kg of body weight) of levofloxacin might be needed to improve its activity. Doses in the range of 17 to 20 mg/kg showed good target attainment for MICs from 0.25 to 0.50. At an MIC of 2, poor target attainment was observed across all doses. This LSS for levofloxacin can be used for therapeutic drug monitoring and for future pharmacokinetic/ pharmacodynamic studies.T uberculosis (TB) is the second leading cause of death from an infectious disease, behind HIV. In 2012, 8.6 million people developed TB, and 1.3 million died from it. Also, multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB are on the rise. The WHO estimates that about 5% of the new TB cases globally are caused by MDR-TB, and of those, 9% are XDR-TB (1). This indicates that the current treatment is not adequate. The standard treatment of TB consists of rifampin, isoniazid, pyrazinamide, and ethambutol for 2 months, followed by rifampin and isoniazid for 4 to 7 months. The success rate for this regimen is relatively high (greater than 95%) based on per-protocol analyses of the initial clinical trials (2, 3). However, TB is still a worldwide pandemic, and even in the United States, with its excellent TB control efforts, only about 89% of patients complete treatment within 12 months, not 6 (4). Lack of adherence may lead to treatment failure and development of MDR TB.The treatment of MDR-TB currently requires treatment for a minimum of 18 months with at least 4 drugs, including an injectable (aminoglycoside or polypeptide). Examples of second-line drugs used for MDR-TB include ethionamide, cycloserine, and p-aminosalicylic acid. Drugs...

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“…A limited sampling strategy (LSS) is a method that requires fewer, usually one to three, optimally timed samples to accurately estimate the AUC. LSSs can be determined using both multiple linear regression and the Bayesian approach (18). The ease of multiple linear regression is that the resulting equation can estimate AUC with the obtained drug concentrations, although the samples should be timed exactly.…”

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confidence: 99%

“…The ease of multiple linear regression is that the resulting equation can estimate AUC with the obtained drug concentrations, although the samples should be timed exactly. The Bayesian approach is less rigid with timing of the samples and will generally result in more accurate estimates of the AUC, since it includes the population pharmacokinetic model, patient characteristics, sampling errors, and assay errors (15,18). However, the Bayesian method requires pharmacokinetic modeling software that is not available to all clinical centers in settings endemic for MDR-TB and RR-TB.…”

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confidence: 99%

Population Pharmacokinetic Model and Limited Sampling Strategies for Personalized Dosing of Levofloxacin in Tuberculosis Patients

Elsen

Sturkenboom

Boveneind-Vrubleuskaya

et al. 2018

Antimicrob Agents Chemother

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Levofloxacin is an antituberculosis drug with substantial interindividual pharmacokinetic variability; therapeutic drug monitoring (TDM) could therefore be helpful to improve treatment results. TDM would be more feasible with limited sampling strategies (LSSs), a method to estimate the area under the concentration curve for the 24-h dosing interval (AUC0–24) by using a limited number of samples. This study aimed to develop a population pharmacokinetic (popPK) model of levofloxacin in tuberculosis patients, along with LSSs using a Bayesian and multiple linear regression approach. The popPK model and Bayesian LSS were developed using data from 30 patients and externally validated with 20 patients. The LSS based on multiple linear regression was internally validated using jackknife analysis. Only clinically suitable LSSs (maximum time span, 8 h; minimum interval, 1 h; 1 to 3 samples) were tested. Performance criteria were root-mean-square error (RMSE) of <15%, mean prediction error (MPE) of <5%, and r2 value of >0.95. A one-compartment model with lag time best described the data while only slightly underestimating the AUC0–24 (mean, −7.9%; standard error [SE], 1.7%). The Bayesian LSS using 0- and 5-h postdose samples (RMSE, 8.8%; MPE, 0.42%; r2 = 0.957) adequately estimated the AUC0–24, with a mean underestimation of −4.4% (SE, 2.7%). The multiple linear regression LSS using 0- and 4-h postdose samples (RMSE, 7.0%; MPE, 5.5%; r2 = 0.977) was internally validated, with a mean underestimation of −0.46% (SE, 2.0%). In this study, we successfully developed a popPK model and two LSSs that could be implemented in clinical practice to assist TDM of levofloxacin. (This study has been registered at ClinicalTrials.gov under identifier NCT01918397.)

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Limited-Sampling Strategies for Anti-Infective Agents: Systematic Review

Cited by 6 publications

References 42 publications

Clinical Pharmacokinetics of Clopidogrel and Its Metabolites in Patients with Cardiovascular Diseases

Clinical Pharmacokinetics of Clopidogrel and Its Metabolites in Patients with Cardiovascular Diseases

Limited Sampling Strategy and Target Attainment Analysis for Levofloxacin in Patients with Tuberculosis

Population Pharmacokinetic Model and Limited Sampling Strategies for Personalized Dosing of Levofloxacin in Tuberculosis Patients

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