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An important determinant of the value of quantitative neuroimaging studies is the reliability of the derived information, which is a function of the data collection conditions. Near infrared spectroscopy (NIRS) and electroencelphalography are independent sensing domains that are well suited to explore principal elements of the brain's response to neuroactivation, and whose integration supports development of compact, even wearable, systems suitable for use in open environments. In an effort to maximize the translatability and utility of such resources, we have established an experimental laboratory testbed that supports measures and analysis of simulated macroscopic bioelectric and hemodynamic responses of the brain. Principal elements of the testbed include 1) a programmable anthropomorphic head phantom containing a multisignal source array embedded within a matrix that approximates the background optical and bioelectric properties of the brain, 2) integrated translatable headgear that support multimodal studies, and 3) an integrated data analysis environment that supports anatomically based mapping of experiment-derived measures that are directly and not directly observable. Here, we present a description of system components and fabrication, an overview of the analysis environment, and findings from a representative study that document the ability to experimentally validate effective connectivity models based on NIRS tomography.

In this study, the pharmacokinetics of several formulations of aspirin were examined: soluble aspirin, mouth-dispersible aspirin, plain aspirin and enteric-coated aspirin granules. Blood samples were taken at frequent intervals for 24 hours after single dosing in 12 healthy volunteers and Tmax, Cmax and t1/2 measured. Cmax was significantly higher for soluble aspirin than for the other formulations and the t1/2 was shorter. The results show the rapid absorption of aspirin from a soluble formulation compared with that from plain aspirin or enteric-coated aspirin granules. Recommendations to treat patients suspected of having a heart attack as soon as possible with aspirin are now widely accepted and the present study would suggest that soluble aspirin should be the aspirin of choice in this situation.

In this study, the bioavailability of aspirin and paracetamol was compared in plain and soluble combination formulations in fasting, healthy volunteers. Blood samples were taken and Cmax, Tmax and AUC measured at various times following administration of single doses of the two formulations in 12 subjects. The rapidity of uptake of aspirin following administration of a soluble formulation suggests significant absorption from the stomach. There was no significant difference in the pharmacokinetic parameters of paracetamol derived from a soluble or plain formulation. A comparison of the uptake of aspirin from the soluble aspirin formulation with paracetamol from either plain or soluble tablets showed that aspirin entered the plasma and achieved peak levels significantly more quickly. However, the half life of paracetamol was significantly longer than that of aspirin. These findings suggest that onset of analgesia should be more rapid following dosing with soluble aspirin, a conclusion supported by comparative efficacy studies conducted with differing formulations of aspirin.

The comparative bioavailability of cimetidine in cimetidine-alginate combinations has been investigated in twelve healthy volunteers in an open crossover study. Each volunteer received a single oral dose of a commercially available alginate-cimetidine combination tablet (Algitec) or cimetidine tablets (Tagamet), coadministered with a commercially available alginate reflux suppressant liquid or tablet (Gaviscon). No significant differences were observed between treatments for Cmax, tmax, AUC0–12 or AUC0-∞. The study demonstrated equivalent bioavailability of cimetidine when administered separately with alginate products and as a fixed dose combination product.

A high pressure liquid chromatographic assay was developed for simultaneous measurement of the plasma levels of tolmesoxide and its principal metabolite, RX71112. The assay was used to study the disposition of intravenous and oral tolmesoxide in ten normotensive subjects. Two exponential terms were required to describe the disposition of the drug following intravenous administration, whilst a single exponential term sufficed to account for the decay in the plasma concentration after oral administration. The bioavailability of oral tolmesoxide from capsules averaged 84.5% and was independent of dose. The mean half-life after i.v. dosing was 2.6 h (+/- 0.3 SEM) compared to values of 1.9 h (+/- 0.1 SEM) and 2.7 h (+/- 0.5 SEM) following 200 and 400 mg oral doses respectively. In all subjects RX71112 appeared in plasma shortly after tolmesoxide following both routes of administration. The terminal half-life of the metabolite was significantly longer than tolmesoxide with a mean value of 4.9 h (+/- 0.9 SEM) following the 200 mg oral dose of tolmesoxide. The binding of tolmesoxide and RX71112 at therapeutic plasma concentration was 36.8% (+/- 0.5 SEM) and 58.5% (+/- 0.3 SEM) and this remained unchanged at higher concentrations.

A high performance liquid chromatographic method was developed for the quantitative determination of idazoxan in plasma. The assay was used to study the disposition of the drug after intravenous infusion and oral administration to five normal subjects. After i.v. administration the kinetics could be described by a two compartment model with a mean elimination half life of 4.20 h. The mean calculated volume of distribution during the elimination phase was 3.20 l/kg-1 and the mean plasma clearance was 824 ml min-1. After oral administration a lag period before onset of absorption was observed in all five volunteers, the plasma levels declining monoexponentially from the peak concentration with a mean elimination half life of 5.58 h. The absolute availability varied between 26% and 41% with a mean value of 34%. In-vitro measurements produced a blood/plasma ratio of 1.3 for idazoxan.

The plasma concentration of the anti-inflammatory drug fenclofenac was investigated in volunteers following single oral doses of 200, 500 and 600 mg, as well as multiple doses of 600mg b.i.d. over five days, using gas chromatography with electron capture detection. The pharmacokinetic parameters derived were independent of dose, and the terminal half-life, t1/2, varied independently of dose between 20 and 38 hours (27.23 +/- 1.8 at 600mg). The apparent volume of distribution (Vd area) had similar values at doses of 200, 500 and 600mg of 15.2 +/- 2.6, 18.2 +/- 1.5 and 14.7 +/- 1.7 litres respectively. These small volumes of distribution indicate that fenclofenac distributes mainly into extracellular space. A mean peak plasma concentration of 63.5 +/- 4.6microgram/ml developed after 3 to4 hours following a single 600mg dose whilst a mean steady state plasma concentration (600mg b.i.d.) of 86.9 +/- 5.7 microgram/ml was achieved within four days, and this decayed with a mean terminal half-life of 25.9 +/- 4.2 hours.