An adaptive grid non-parametric approach to pharmacokinetic and dynamic (PK/PD) population models

Leary, Robert; Jelliffe, Roger W.; Schumitzky, Alan; Guilder, Michael Van

doi:10.1109/cbms.2001.941750

Cited by 123 publications

(119 citation statements)

References 4 publications

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“…Within Pmetrics, we used the nonparametric adaptive grid (NPAG) algorithm (19,21,22) to build a population pharmacokinetic model for the pooled data sets, referred to here as the data set. On the basis of the prior work of numerous authors, as reviewed by Marsot et al (23), we used a two-compartment model for vancomycin, parameterized with linear elimination (K e ) from the central compartment with a volume (V c ) and linear transfer to (K CP ) and from (K PC ) the peripheral compartment.…”

Section: Methodsmentioning

confidence: 99%

Are Vancomycin Trough Concentrations Adequate for Optimal Dosing?

Neely

Youn

Jones

et al. 2014

Antimicrob Agents Chemother

323

351

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eThe current vancomycin therapeutic guidelines recommend the use of only trough concentrations to manage the dosing of adults with Staphylococcus aureus infections. Both vancomycin efficacy and toxicity are likely to be related to the area under the plasma concentration-time curve (AUC). We assembled richly sampled vancomycin pharmacokinetic data from three studies comprising 47 adults with various levels of renal function. With Pmetrics, the nonparametric population modeling package for R, we compared AUCs estimated from models derived from trough-only and peak-trough depleted versions of the full data set and characterized the relationship between the vancomycin trough concentration and AUC. The trough-only and peak-trough depleted data sets underestimated the true AUCs compared to the full model by a mean (95% confidence interval) of 23% (11 to 33%; P ‫؍‬ 0.0001) and 14% (7 to 19%; P < 0.0001), respectively. In contrast, using the full model as a Bayesian prior with troughonly data allowed 97% (93 to 102%; P ‫؍‬ 0.23) accurate AUC estimation. On the basis of 5,000 profiles simulated from the full model, among adults with normal renal function and a therapeutic AUC of >400 mg · h/liter for an organism for which the vancomycin MIC is 1 mg/liter, approximately 60% are expected to have a trough concentration below the suggested minimum target of 15 mg/liter for serious infections, which could result in needlessly increased doses and a risk of toxicity. Our data indicate that adjustment of vancomycin doses on the basis of trough concentrations without a Bayesian tool results in poor achievement of maximally safe and effective drug exposures in plasma and that many adults can have an adequate vancomycin AUC with a trough concentration of <15 mg/liter.

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Section: Methodsmentioning

confidence: 99%

Are Vancomycin Trough Concentrations Adequate for Optimal Dosing?

Neely

Youn

Jones

et al. 2014

Antimicrob Agents Chemother

323

351

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“…Pharmacokinetic parameters for anidulafungin and voriconazole were determined by population methodology, using the program nonparametric adaptive grid (NPAG) with adaptive gamma (14). A standard two-compartment pharmacokinetic model was used, with zero-order time-delimited input and first-order elimination from the central compartment.…”

Section: Methodsmentioning

confidence: 99%

“…Combination therapy with the echinocandins and triazoles may be more active against invasive aspergillosis than therapy with a single agent alone (10,26). The echinocandins are a class of semisynthetic lipopeptide antifungal compounds that inhibit synthesis of (133)-␤-D-glucan, a key component of the cell walls of most pathogenic fungi (6,14).…”

mentioning

confidence: 99%

Combination Therapy in Treatment of Experimental Pulmonary Aspergillosis: In Vitro and In Vivo Correlations of the Concentration- and Dose- Dependent Interactions between Anidulafungin and Voriconazole by Bliss Independence Drug Interaction Analysis

Petraitis

Petraitienė

Hope

et al. 2009

Antimicrob Agents Chemother

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We studied the antifungal activity of anidulafungin (AFG) in combination with voriconazole (VRC) against experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits and further explored the in vitro and in vivo correlations by using Bliss independence drug interaction analysis. Treatment groups consisted of those receiving AFG at 5 (AFG5 group) and 10 (AFG10 group) mg/kg of body weight/day, VRC at 10 mg/kg every 8 h (VRC group), AFG5 plus VRC (AFG5؉VRC group), and AFG10 plus VRC (AFG10؉VRC group) and untreated controls. Survival throughout the study was 60% for the AFG5؉VRC group, 50% for the VRC group, 27% for the AFG10؉VRC group, 22% for the AFG5 group, 18% for the AFG10 group, and 0% for control rabbits (P < 0.001). There was a significant reduction of organism-mediated pulmonary injury, measured by infarct scores, lung weights, residual fungal burdens, and galactomannan indexes, in AFG5؉VRC-treated rabbits versus those treated with AFG5 and VRC alone (P < 0.05). In comparison, AFG10؉VRC significantly lowered only infarct scores and lung weights in comparison to those of AFG10-treated animals (P < 0.05). AFG10؉VRC showed no significant difference in other outcome variables. Significant Bliss synergy was found in vivo between AFG5 and VRC, with observed effects being 24 to 30% higher than expected levels if the drugs were acting independently. These synergistic interactions were also found between AFG and VRC in vitro. However, for AFG10؉VRC, only independence and antagonism were observed among the outcome variables. We concluded that the combination of AFG with VRC in treatment of experimental IPA in persistently neutropenic rabbits was independent to synergistic at a dosage of 5 mg/kg/day but independent to antagonistic at 10 mg/kg/day, as assessed by Bliss independence analysis, suggesting that higher dosages of an echinocandin may be deleterious to the combination.

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“…Algoritma NPEM ini mempunyai 2 fase yaitu pencarian likelihood dan maksimasi likelihood [1]. Pada fase maksimasi likelihood, NPEM menggunakan metode gaussian quadrature yang terbukti kurang efisien dibandingkan dengan metode maksimasi likelihood menggunakan NPAG (Non Parametric Adaptive Grid) yang dipadukan dengan metode newton.…”

Section: Pendahuluanunclassified

“…Pada model satu kompartemen, persamaan untuk meramalkan konsentrasi obat teramati (Y) untuk pada berbagai waktu (t) pengambilan sampel setelah pemberian obat dinyatakan dalam model struktural berikut [1]:…”

Section: Gambar 1 Single Compartment Modelunclassified

Penggunaan Algoritma Newton – Raphson Untuk Membuat Software Penentuan Dosis Obat

Gunawan¹

2010

informatika

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ABSTRAK:Software USCPACK buatan University of Carolina merupakan salah satu pelopor dimungkinkannya penentuan dosis obat persatuan waktu tertentu untuk pasien secara umum menggunakan komputer. Software ini bekerja dengan menggunakan metode dasar Bayesian. Algoritma yang digunakan oleh software ini adalah NPEM (Non Parametric Expectation Maximization). Setelah mengetahui cara kerja dari USCPACK maka dibuatlah sebuah software pendosisan obat menggunakan algoritma non parametrik lain selain NPEM. Paper ini akan membahas pembuatan software pendosisan obat menggunakan algoritma newton -raphson dalam penentuan dosis obat terkomputerisasi.

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An adaptive grid non-parametric approach to pharmacokinetic and dynamic (PK/PD) population models

Cited by 123 publications

References 4 publications

Are Vancomycin Trough Concentrations Adequate for Optimal Dosing?

Are Vancomycin Trough Concentrations Adequate for Optimal Dosing?

Combination Therapy in Treatment of Experimental Pulmonary Aspergillosis: In Vitro and In Vivo Correlations of the Concentration- and Dose- Dependent Interactions between Anidulafungin and Voriconazole by Bliss Independence Drug Interaction Analysis

Penggunaan Algoritma Newton – Raphson Untuk Membuat Software Penentuan Dosis Obat

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