Bayesian Parameter Estimation and Population Pharmacokinetics

Thomson, A H; Whiting, B.

doi:10.2165/00003088-199222060-00004

Cited by 131 publications

(61 citation statements)

References 148 publications

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“…[1][2][3][4][5] One of the clinical benefits of this estimation method is that it allows individual pharmacokinetic parameters (individual parameters) to be estimated using only a few blood concentrations. Attempts have been made to apply this estimation method to cases receiving high-dose methotrexate (HD-MTX), which is one of the most widely used anticancer drugs.…”

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confidence: 99%

Developing Population Pharmacokinetic Parameters for High-Dose Methotrexate Therapy: Implication of Correlations among Developed Parameters for Individual Parameter Estimation Using the Bayesian Least-Squares Method

Watanabe

Fukuoka

Takeuchi

et al. 2014

Biological & Pharmaceutical Bulletin

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Bayesian estimation enables the individual pharmacokinetic parameters of the medication administrated to be estimated using only a few blood concentrations. Due to wide inter-individual variability in the pharmacokinetics of methotrexate (MTX), the concentration of MTX needs to be frequently determined during high-dose MTX therapy in order to prevent toxic adverse events. To apply the benefits of Bayesian estimation to cases treated with this therapy, we attempted to develop an estimation method using the Bayesian leastsquares method, which is commonly used for therapeutic monitoring in a clinical setting. Because this method hypothesizes independency among population pharmacokinetic parameters, we focused on correlations among population pharmacokinetic parameters used to estimate individual parameters. A two-compartment model adequately described the observed concentration of MTX. The individual pharmacokinetic parameters of MTX were estimated in 57 cases using the maximum likelihood method. Among the available parameters accounting for a 2-compartment model, V 1 , k 10 , k 12 , and k 21 were found to be the combination showing the weakest correlations, which indicated that this combination was best suited to the Bayesian least-squares method. Using this combination of population pharmacokinetic parameters, Bayesian estimation provided an accurate estimation of individual parameters. In addition, we demonstrated that the degree of correlation among population pharmacokinetic parameters used in the estimation affected the precision of the estimates. This result highlights the necessity of assessing correlations among the population pharmacokinetic parameters used in the Bayesian least-squares method.

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confidence: 99%

Developing Population Pharmacokinetic Parameters for High-Dose Methotrexate Therapy: Implication of Correlations among Developed Parameters for Individual Parameter Estimation Using the Bayesian Least-Squares Method

Watanabe

Fukuoka

Takeuchi

et al. 2014

Biological & Pharmaceutical Bulletin

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“…PK parameter values and their interindividual variability can be determined even when only sparse blood samples are available from a homogeneous or heterogeneous population. Such methodologies can be used even if only one concentration measurement per patient is available (41).…”

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confidence: 99%

Population Pharmacokinetics of Pyrimethamine and Sulfadoxine in Children Treated for Congenital Toxoplasmosis

Corvaisier¹,

Charpiat²,

Mounier

et al. 2004

Antimicrob Agents Chemother

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The population pharmacokinetics of pyrimethamine (PYR) and sulfadoxine (SDX) for a group of 32 children with congenital toxoplasmosis was investigated by nonparametric modeling analysis. A one-compartment model was used as the structural model, and individual pharmacokinetic parameters were estimated by Bayesian modeling. PYR (1.25 mg/kg of body weight) and SDX (25 mg/kg) were administered orally every 10 days for 1 year, with adjustment of the dose to body weight every 3 months. Drug concentrations were measured by high-performance liquid chromatography. A total of 101 measurements in serum were available for both drugs. Mean absorption rate constants, volumes of distribution, elimination rate constants, and half-lives were 0.915 h ؊1 , 4.379 liters/kg, 0.00839 h ؊1 , and 5.5 days for PYR and 1.659 h ؊1 , 0.392 liters/kg, 0.00526 h ؊1 , and 6.6 days for SDX, respectively. Wide interindividual variability was observed. The estimated minimum and maximum concentrations of PYR in serum differed 8-and 25-fold among patients, respectively, and those of SDX differed 4-and 5-fold, respectively. Increases in the concentration of PYR were observed for eight children, and increases in the SDX concentration were observed for seven children. Serum PYR-SDX concentrations are unpredictable even when the dose is standardized for body weight. The concentrations of the PYR-SDX combination that are most efficacious for children have not yet been established. A model such as ours, associated with long-term follow-up, is needed to study the correlation between exposure to these two drugs and clinical outcome in children.Toxoplasma gondii is a ubiquitous intracellular protozoan parasite. Infection during pregnancy can result in fetal infection, leading to severe congenital defects such as hydrocephalus, mental retardation, and retinochoroiditis that may be present at birth or may develop later in life (36). Although no well-controlled clinical trials have been carried out to assess its efficacy and safety in children, early treatment is believed to prevent late-onset sequelae. A bibliographical analysis revealed up to 20 different therapeutic antiparasitic regimens (27). Most of them included courses of a combination of pyrimethamine (PYR) and a sulfonamide (sulfadiazine or sulfadoxine [SDX]). However, pharmacokinetic (PK) data for these drugs are scarce, especially for pediatric populations (6,17,23,48), mainly because of the reluctance to pursue PK studies on children. Consequently, many therapeutic agents, such as PYR and SDX, have not been studied adequately in children (24). However, for the past 2 decades, this problem has been addressed by use of the population-based PK approach and the Bayesian method. PK parameter values and their interindividual variability can be determined even when only sparse blood samples are available from a homogeneous or heterogeneous population. Such methodologies can be used even if only one concentration measurement per patient is available (41).Very few studies of the pharmacokinetics of PYR an...

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“…16 Many examples of the application of these techniques to the individualization of doses for drugs with a narrow therapeutic window have been reported. 17 However, dosage individualization through Bayesian forecasting has never been extensively trialed for any of the immunosuppressive agents.…”

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Toward better outcomes with tacrolimus therapy: Population pharmacokinetics and individualized dosage prediction in adult liver transplantation

Staatz

Willis

Taylor

et al. 2003

Liver Transplantation

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T acrolimus, a potent immunosuppressive agent, has emerged as a valuable therapeutic alternative to cyclosporine after adult liver transplantation. 1 Similar to cyclosporine, tacrolimus has a narrow therapeutic window. 2 Continuous adequate immunosuppression is imperative for maintenance of the graft, whereas overimmunosuppression can lead to serious toxicities, infections, and increased risk for lymphoproliferative disease. It is not possible to give a standard dosing regimen to all adults and achieve concentrations within this narrow therapeutic range. Tacrolimus shows considerable interindividual and intraindividual variability in its pharmacokinetics, with poor correlation between drug dosage and blood concentrations. 2 These factors make defining an optimal dosing schedule for this agent difficult. 3 A number of studies have evaluated the pharmacokinetic properties of tacrolimus. 2 Oral bioavailability of this agent is generally low (ϳ25%), but can vary from 4% to 93%. Tacrolimus binds extensively to erythrocytes and, in plasma, to ␣1-acid glycoprotein and albumin. It is extensively metabolized by the cytochrome P-450 system and subject to P-glycoprotein countertransport. 4 Greater than 95% of tacrolimus is eliminated by the biliary route; renal excretion of the parent drug accounts for less than 1% of total body clearance.To date, the majority of pharmacokinetic studies in adult liver transplant recipients have used a classic approach to data generation. [5][6][7][8][9][10][11][12] Kinetic information has been obtained through multiple blood sampling in small relatively homogenous patient groups during a single dosing interval or during a short time span in the immediate posttransplantation period. Different factors that may alter drug pharmacokinetics have not been investigated simultaneously. Such studies provide little information on interindividual and intraindividual pharmacokinetic variability. Furthermore, kinetic information has been based on immunoassay analysis of tacrolimus blood samples. Such assays are not specific for the parent drug, with reports of significant and variable cross-reactivity of assay antibody with some tacrolimus metabolites. 3 Such assay techniques as liquid chromatography-tandem mass spectrometry

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Bayesian Parameter Estimation and Population Pharmacokinetics

Cited by 131 publications

References 148 publications

Developing Population Pharmacokinetic Parameters for High-Dose Methotrexate Therapy: Implication of Correlations among Developed Parameters for Individual Parameter Estimation Using the Bayesian Least-Squares Method

Developing Population Pharmacokinetic Parameters for High-Dose Methotrexate Therapy: Implication of Correlations among Developed Parameters for Individual Parameter Estimation Using the Bayesian Least-Squares Method

Population Pharmacokinetics of Pyrimethamine and Sulfadoxine in Children Treated for Congenital Toxoplasmosis

Toward better outcomes with tacrolimus therapy: Population pharmacokinetics and individualized dosage prediction in adult liver transplantation

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