An electroencephalographic processing algorithm specifically intended for analysis of cerebral electrical activity

Gregory, Thomas; Pettus, Daniel C.

doi:10.1007/bf01620551

Cited by 63 publications

(14 citation statements)

References 4 publications

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“…Briefly, the electrodes were placed at the locations 11 mm anterior and + 2.5 mm lateral (FI and F) (Gregory & Pettus, 1986 (Rathburn) in a ratio 50/50 with a flow rate of 1.0mlmin-. Retention times were 4.4 and 5.0 min for diazepam and midazolam respectively.…”

Section: Pharmacokinetic-pharmacodynamic Experimentsmentioning

confidence: 99%

“…Two EEG leads (F,-C, and C-Oi) were subjected to on-line aperiodic analysis for quantification, using the Lifescan EEG monitor (Neurometrics Inc., San Diego, U.S.A.). Aperiodic analysis was recently introduced as a new technique to quantify brain electrical activity (Gregory & Pettus, 1986). The aperiodic analysis algorithm calculates the amplitude and period of each EEG signal on a wave by wave basis.…”

Section: Pharmacokinetic-pharmacodynamic Experimentsmentioning

confidence: 99%

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Pharmacokinetic‐pharmacodynamic modelling of the EEG effects of midazolam in individual rats: influence of rate and route of administration

Mandema

Tukker

Danhof³

1991

British J Pharmacology

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Section: Pharmacokinetic-pharmacodynamic Experimentsmentioning

confidence: 99%

Section: Pharmacokinetic-pharmacodynamic Experimentsmentioning

confidence: 99%

Pharmacokinetic‐pharmacodynamic modelling of the EEG effects of midazolam in individual rats: influence of rate and route of administration

Mandema

Tukker

Danhof³

1991

British J Pharmacology

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“…In a series of studies, aimed at the development of a pharmacokinetic-pharmacodynamic drug-drug interaction model for flumazenil and midazolam, we first determined the pharmacokinetics and pharmacodynamics of midazolam (Breimer et al 1990). In that study, the total number of waves in the 12-30Hz frequency range (TNW 12-30), a parameter derived from the EEG with aperiodic analysis (Gregory & Pettus 1986), was used to quantify the effect of midazolam. In the second study we investigated the effect of flumazenil on TNW [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] and determined the pharmacokinetics of this drug (Breimer et al 1989a), demonstrating that flumazenil has no intrinsic effect on TNW 12-30 (Breimer et al 1989b).…”

mentioning

confidence: 99%

Pharmacokinetic-Pharmacodynamic Modelling of the Interaction between Flumazenil and Midazolam in Volunteers by Aperiodic EEG Analysis

Breimer

Burm

Danhof

et al. 1991

Clinical Pharmacokinetics

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The CNS effects resulting from the combined administration of midazolam and flumazenil were studied in 8 healthy volunteers to develop a model of the pharmacokinetic-pharmacodynamic interaction. Electroencephalograms (EEG) were recorded between Fp1-M1 and Fp2-M2. The EEG parameter total number of waves between 12 and 30 Hz (TNW12-30) derived by aperiodic analysis was used to quantify the effect. Following a 15 min baseline EEG recording, infusion of placebo or flumazenil was started. Infusion regimens for flumazenil were designed so that 'steady-state' concentrations of 10 and 20 micrograms/L were obtained. Doses of midazolam 15, 30 and 60 mg over 5 min were given 30 min after the start of placebo infusion (session A) or flumazenil infusion to 10 micrograms/L (session B) or 20 micrograms/L (session C), respectively. Venous blood samples were taken until 8 h after the start of the flumazenil or placebo infusion. A sigmoid maximum effect (Emax) model was used to characterise the relationship between the plasma concentration of midazolam which is in equilibrium with the effect compartment concentration (Cem) [Cem/Kp] and TNW12-30. Within 2 to 5 min of starting the midazolam infusion all subjects fell asleep, with loss of eyelid reflex. They awoke between 25 and 82 min later in all 3 sessions. The mean (+/- SD) plasma drug concentrations of midazolam corresponding to half the maximum increase in TNW12-30 (EC50) were 276 +/- 64, 624 +/- 187 and 1086 +/- 379 micrograms/L in sessions A, B and C, respectively. The half-lives reflecting equilibration between plasma concentration and effect (t1/2ke0), estimated by a nonparametric method, were 2.2 +/- 1.2, 3.3 +/- 3.3 and 2.9 +/- 1.2 min for the 3 different sessions. Emax and N were not affected by flumazenil. In each subject the plot of the average measured steady-state plasma flumazenil concentration versus the EC50 of midazolam showed a linear relationship. The plasma concentration of flumazenil that doubled the EC50 of midazolam (Cf,2) was 6.5 +/- 1.0 micrograms/L. The observed interaction is consistent with the competitive nature of the antagonism of midazolam by flumazenil.

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“…By applying aperiodic analysis (Gregory & Pettus, 1986) the total amplitude in the frequency area of 11.5 to 30 Hz of the fronto-central EEG lead was calculated and used as the descriptor of the drug effect, because this was shown to provide an optimal measure for the effect of midazolam on the central nervous system (Mandema et al, 1991b). More detailed information on the recording and analysis of the EEG are described by Mandema et al (1991a).…”

Section: W11" Macmillan Pressmentioning

confidence: 99%

Pharmacokinetic‐EEG effect relationship of midazolam in aging BN/BiRij rats

Hovinga

Stijnen

Langemeijer

et al. 1992

British J Pharmacology

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1 The purpose of the present investigations was to determine the influence of increasing age on the pharmacokinetics and pharmacodynamics of midazolam in male BN/BiRij rats as an animal model of aging.2 Midazolam was administered intravenously at a dose of 2.5 mg kg-' and its pharmacokinetics were determined on the basis of plasma concentrations as measured by high performance liquid chromatography (h.p.l.c.). Pharmacodynamics were studied using the midazolam-induced changes in the electroencephalogram (EEG) as a measure of the pharmacological effect. Results were evaluated on the basis of stimultaneous pharmacokinetic-pharmacodynamic modelling. In an attempt to differentiate between the effects of aging and of concurrent disease, an extensive clinical biochemical/pathological examination was conducted in individual rats by an independent pathologist. 3 The pharmacokinetics of midazolam were best characterized on the basis of a two exponential model. In the 4-month-old rats the values of the clearance, volume of distribution and elimination half-life were 104 ± 13 ml min-' kg-' (mean ± s.e.mean), 3.4 ± 0.71 kg-1 and 30 + 3 min, respectively.With increasing age, no changes in the pharmacokinetics of midazolam were observed. 4 The pharmacodynamics of midazolam were determined on the basis of the sigmoidal Emax model. In the 4-month-old rats the values of the parameters relative maximum effect, midazolam concentration at half maximum effect and Hill factor were 106 ± 10%, 50 ± 6 lg 1' and 1.6 ± 0.3, respectively. In the group as a whole no significant changes in the pharmacodynamic parameters of midazolam were observed. However, when diseased animals were excluded from the evaluation, a tendency towards a decrease in the midazolam concentration at half maximum effect to 25 ± 14 pg 1-1 was observed in the 36-month-old rats. 5 These findings suggest, that increasing age is associated with a tendency towards an increased brain sensitivity to midazolam, which is reflected in a parallel shift of the concentration vs. EEG effect relationship towards lower concentrations. However, it appears that factors other than age also contribute to interindividual variability in pharmacodynamics, considering the substantial interindividual variability within certain age groups.

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An electroencephalographic processing algorithm specifically intended for analysis of cerebral electrical activity

Cited by 63 publications

References 4 publications

Pharmacokinetic‐pharmacodynamic modelling of the EEG effects of midazolam in individual rats: influence of rate and route of administration

Pharmacokinetic‐pharmacodynamic modelling of the EEG effects of midazolam in individual rats: influence of rate and route of administration

Pharmacokinetic-Pharmacodynamic Modelling of the Interaction between Flumazenil and Midazolam in Volunteers by Aperiodic EEG Analysis

Pharmacokinetic‐EEG effect relationship of midazolam in aging BN/BiRij rats

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