### Abstract

A systematic approach to individualizing the phenytoin (PHT) dose from a previous dose (D) and steady-state concentration (C(ss)) pair was established by the combined use of two methods based on recently reported population pharmacokinetic parameters. This system applies the Michaelis-Menten equation to the initial data pair (D(t)-C(ss1)) and solves for (a) maximum metabolic rate constant (V(max)) assuming the population mean for the Michaelis constant (K(m)) (method 1), and (b) K(m) assuming the population mean for V(max) (method 2). The derived estimates of V(max) and K(m) are then put through a series of filters, which results in the selection of method 1 and/or method 2 or allocation of a third category that needs further evaluation. A simulation study was performed to find a series of filters. The presented approach was applied retrospectively to the patients' data of 35 sets. Accurate predictions of the C(ss) error within 5 μg/ml were obtained in 84% of the 25 cases, and in 30% of the 10 cases excluded. This systematic approach gives better prediction performance in mean error, mean absolute error, and root mean square error than a Bayesian feedback method.

Original language | English |
---|---|

Pages (from-to) | 12-18 |

Number of pages | 7 |

Journal | Therapeutic Drug Monitoring |

Volume | 17 |

Issue number | 1 |

Publication status | Published - 1995 |

Externally published | Yes |

### Fingerprint

### Keywords

- Dosage regimen
- Graphic estimation
- Phenytoin
- Systematic approach

### ASJC Scopus subject areas

- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Health, Toxicology and Mutagenesis
- Pharmacology (medical)
- Public Health, Environmental and Occupational Health
- Pharmacology
- Toxicology

### Cite this

*Therapeutic Drug Monitoring*,

*17*(1), 12-18.

**Systematic approach to a dosage regimen for phenytoin based on one-point, steady-state plasma concentration.** / Nakashima, E.; Matsushita, R.; Kido, H.; Nakamura, M.; Asahi, M.; Ichimura, F.

Research output: Contribution to journal › Article

*Therapeutic Drug Monitoring*, vol. 17, no. 1, pp. 12-18.

}

TY - JOUR

T1 - Systematic approach to a dosage regimen for phenytoin based on one-point, steady-state plasma concentration

AU - Nakashima, E.

AU - Matsushita, R.

AU - Kido, H.

AU - Nakamura, M.

AU - Asahi, M.

AU - Ichimura, F.

PY - 1995

Y1 - 1995

N2 - A systematic approach to individualizing the phenytoin (PHT) dose from a previous dose (D) and steady-state concentration (C(ss)) pair was established by the combined use of two methods based on recently reported population pharmacokinetic parameters. This system applies the Michaelis-Menten equation to the initial data pair (D(t)-C(ss1)) and solves for (a) maximum metabolic rate constant (V(max)) assuming the population mean for the Michaelis constant (K(m)) (method 1), and (b) K(m) assuming the population mean for V(max) (method 2). The derived estimates of V(max) and K(m) are then put through a series of filters, which results in the selection of method 1 and/or method 2 or allocation of a third category that needs further evaluation. A simulation study was performed to find a series of filters. The presented approach was applied retrospectively to the patients' data of 35 sets. Accurate predictions of the C(ss) error within 5 μg/ml were obtained in 84% of the 25 cases, and in 30% of the 10 cases excluded. This systematic approach gives better prediction performance in mean error, mean absolute error, and root mean square error than a Bayesian feedback method.

AB - A systematic approach to individualizing the phenytoin (PHT) dose from a previous dose (D) and steady-state concentration (C(ss)) pair was established by the combined use of two methods based on recently reported population pharmacokinetic parameters. This system applies the Michaelis-Menten equation to the initial data pair (D(t)-C(ss1)) and solves for (a) maximum metabolic rate constant (V(max)) assuming the population mean for the Michaelis constant (K(m)) (method 1), and (b) K(m) assuming the population mean for V(max) (method 2). The derived estimates of V(max) and K(m) are then put through a series of filters, which results in the selection of method 1 and/or method 2 or allocation of a third category that needs further evaluation. A simulation study was performed to find a series of filters. The presented approach was applied retrospectively to the patients' data of 35 sets. Accurate predictions of the C(ss) error within 5 μg/ml were obtained in 84% of the 25 cases, and in 30% of the 10 cases excluded. This systematic approach gives better prediction performance in mean error, mean absolute error, and root mean square error than a Bayesian feedback method.

KW - Dosage regimen

KW - Graphic estimation

KW - Phenytoin

KW - Systematic approach

UR - http://www.scopus.com/inward/record.url?scp=0028887315&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028887315&partnerID=8YFLogxK

M3 - Article

C2 - 7725371

AN - SCOPUS:0028887315

VL - 17

SP - 12

EP - 18

JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

SN - 0163-4356

IS - 1

ER -