Search PubMed⌕ Search

Biomedical subjects

T J Gillespie

Publications and source records attributed to T J Gillespie.

26 records · Page 2Linked to original sources

Age and fentanyl pharmacokinetics.

Fentanyl pharmacokinetics was compared in two groups of adult patients, one group (n = 5) aged less than 50 years, and one group (n = 4) aged greater than 60 years. Despite equivalent doses of fentanyl (10 microgram/kg IV), serum drug concentrations were significantly higher in the older patient group. This was reflected by a prolonged terminal elimination half-life in the elderly compared with the younger patients (945 versus 265 minutes, respectively, p less than 0.005). Volumes of the central compartment and volumes of drug distribution were similar in both patient groups. However, drug clearance was markedly decreased in the elderly (265 versus 991 ml/min, p less than 0.005). These data suggest that a given dose of fentanyl will be clinically effective for a longer period in older patients than in younger patients.

Adult↗

Sensitive gas chromatographic determination of trifluoperazine in human plasma.

Plasma trifluoperazine levels of patients taking a single 20 mg dose of trifluoperazine were measured by a sensitive and linear method. The low detection limit of 0.1 ng/ml plasma was obtained through use of a highly sensitive nitrogen-phosphorus detector combined with an efficient extraction method. Recovery of trifluoperazine to human plasma was 96%. Data are presented on the stability of trifluoperazine in refrigerated human plasma.

Chromatography, Gas↗

Ethanol treatment alters beta-endorphin metabolism by purified synaptosomal plasma membranes.

Ethanol administration has been shown to affect beta-endorphin (beta-E) levels in most brain areas. Chronic ethanol treatment has also lead to changes in the levels of Met- and Leu-enkephalin which may be due to recent finding that enkephalin A activity is significantly altered. To determine if proteolytic enzymes responsible for beta-E metabolism at the pSPM are also altered, we studied the effect of chronic ethanol (7% v/v; 8 days) administration on in vitro central beta-E metabolism in male C57/BL mice. Purified SPM was time-course incubated with beta-E (20 microM) for 30-120 min and subjected to HPLC analyses for determination of beta-endorphin and related fragments. Chronic ethanol significantly reduced the half-life for beta-E at the pSPM (T1/2 = 50/min) versus controls (T1/2 = 100.4 min). Chronic ethanol also caused significant accumulation of the behaviorally active alpha- and gamma-type endorphins formed at the pSPM. These results suggest that chronic ethanol treatment leads to an increase in the activity of peptidases responsible for beta-E metabolism at pSPM leading to an increased formation of both alpha- and gamma-type endorphins which may affect alcohol related behaviors.

Animals↗

Peptide fragments derived from the beta-chain of hemoglobin (hemorphins) are centrally active in vivo.

A novel tetrapeptide (hemorphin-4) and pentapeptide (hemorphin-5), derived from the beta-chain of hemoglobin, were synthesized by solid-phase methodology, purified and the amino acid sequences confirmed. The central (ICV) effects of hemorphin-4 and -5 were studied in two models of phasic and tonic nociception, the mouse warm water tail-flick assay and hindpaw formalin assay, respectively. Additionally, two physiological endpoints, central modulation of bladder motility and central effects on intestinal propulsion, were studied in rats and mice, respectively. In the tail-flick assay, both peptides (40-100 nmoles) produced a dose-related naloxone-reversible antinociceptive effect when tested 10 min after peptide administration, with the tetrapeptide being slightly more potent than the pentapeptide. No effect was noted for either peptide using the tonic nociception assay, except at a dose of 150 nmoles for hemorphin-5. Inhibition of gastrointestinal propulsion was also not affected by either peptide. However, both peptides (10-40 nmoles) inhibited micturition contractions in a dose-related and naloxone-reversible fashion, with the tetrapeptide being twice as potent as the pentapeptide. These findings provide evidence that hemorphin-4 and -5 exert naloxone-reversible opioid actions in vivo and, therefore, may be physiologically important blood-borne peptides.

Analgesics↗

Gas chromatographic determination of fentanyl and its analogues in human plasma.

There is currently no published chromatographic assay for the fentanyl family of analgesics. This study reports the development of a sensitive, precise, and accurate gas chromatographic method for the determination of fentanyl and its analogues in human plasma. Sensitivity attained for fentanyl and sufentanil was 0.1 ng/mL plasma with an average coefficient of variation of 4.5%. Calibration curve correlation coefficients of 0.99% or greater were consistently obtained. Average recovery of drug into the final extract exceeded 80% and was independent of fentanyl concentration. The required degree of specificity was obtained by selective extraction, use of the nitrogen/phosphorous detector, and chromatographic resolution. This method appears suitable for clinical studies of fentanyl and its derivatives in man.

Alfentanil↗

Identification and quantification of alpha-methylfentanyl in post mortem specimens.

Alpha-methylfentanyl, a potent and illicit narcotic, was isolated and identified in post mortem tissues of a drug overdose victim. Quantification was performed with a gas chromatograph equipped with a nitrogen-phosphorous detector (GC/NPD). Alpha-methylfentanyl concentrations of 78 ng/g, 3.1 ng/mL, and 6.4 ng/mL were obtained for liver, blood, and bile, respectively. Conclusive identification of methylfentanyl was accomplished by mass spectrometry. Despropionylmethylfentanyl was also detected in the extracts of the victim's tissues.

Adult↗

A micrometeorological technique to monitor total hydrocarbon emissions from landfarms to the atmosphere.

Landfarming is used to treat petroleum hydrocarbon-contaminated soils and a variety of waste streams from industrial operations. Wastes are applied to a soil surface and indigenous soil microorganisms utilize the hydrocarbons in the applied waste as a carbon source for metabolism, thereby biodegrading the applied material. Concerns have been expressed that abiotic losses, such as volatilization, play a significant role in hydrocarbon reduction within the soil. To assist in better defining atmospheric releases of total hydrocarbons from landfarms treating petroleum hydrocarbons, a flux gradient micrometeorological approach was developed and integrated with a custom-built total hydrocarbon detector, and a novel air sampling system and averaging algorithm. The micrometeorological technique offers unobtrusive spatially averaged real-time continuous measurements, thereby providing a time history of emissions. This provides opportunities to investigate mechanisms controlling emissions and to evaluate landfarm management strategies. The versatility of the technique is illustrated through measurements performed at a remote landfarm used to treat diesel fuel-contaminated soil in northern Ontario and during routine operations at two active refinery landfarms in southwestern Ontario.

Agriculture↗